ascorbic-acid and Breast-Neoplasms

Antioxidant vitamin supplements (AVSs) are widely used among breast cancer survivors. Whether post-diagnosis use of AVSs would impair cancer survival is unclear. To assess the association between breast cancer survival and post-diagnosis AVSs use. We performed a literature search using PubMed, Cochrane Library, and Embase from their inception to October 1, 2020. Studies that investigated the association between breast cancer survival and post-diagnosis AVS use included. The AVSs included 1 or more of the following: vitamin A, C, or E. The meta-analysis included 8 studies with 17,062 patients. There was no significant difference between AVS use or not after diagnosis (HR 0.92, 95% CI 0•82-1•03) or during chemotherapy (HR 1.15, 95% CI 0.78-1.68) in overall survival (OS). Whenever during chemotherapy or after diagnosis, AVS users had a worse prognosis in the later studies. There was no significant inverse association between post-diagnosis vitamin A or E supplements use and OS. Vitamin C intake after breast cancer diagnosis was significantly associated with better OS (HR 0.84, 95% CI 0.76-0.93). Our findings suggest that post-diagnosis AVSs use would not worsen breast cancer survival, while vitamin C use after diagnosis might benefit OS. The discrepancy of survivals associated with post-diagnosis AVS use between earlier and later studies may cast doubt on the recommendation on guidelines. RCTs with large sample sizes are needed.

Topics: Antioxidants; Ascorbic Acid; Breast Neoplasms; Cancer Survivors; Dietary Supplements; Female; Health Status; Humans; Primary Prevention; Vitamin A; Vitamin E

Circulating vitamin C concentrations have been associated with several cancers in observational studies, but little is known about the causal direction of the associations. This study aims to explore the potential causal relationship between circulating vitamin C and risk of five most common cancers in Europe.. We used summary-level data for genetic variants associated with plasma vitamin C in a large vitamin C genome-wide association study (GWAS) meta-analysis on 52,018 Europeans, and the corresponding associations with lung, breast, prostate, colon, and rectal cancer from GWAS consortia including up to 870,984 participants of European ancestry. We performed two-sample, bi-directional Mendelian randomization (MR) analyses using inverse-variance-weighted method as the primary approach, while using 6 additional methods (e.g., MR-Egger, weighted median-based, and mode-based methods) as sensitivity analysis to detect and adjust for pleiotropy. We also conducted a meta-analysis of prospective cohort studies and randomized controlled trials to examine the association of vitamin C intakes with cancer outcomes.. The MR analysis showed no evidence of a causal association of circulating vitamin C concentration with any examined cancer. Although the odds ratio (OR) per one standard deviation increase in genetically predicted circulating vitamin C concentration was 1.34 (95% confidence interval 1.14 to 1.57) for breast cancer in the UK Biobank, this association could not be replicated in the Breast Cancer Association Consortium with an OR of 1.05 (0.94 to 1.17). Smoking initiation, as a positive control for our reverse MR analysis, showed a negative association with circulating vitamin C concentration. However, there was no strong evidence of a causal association of any examined cancer with circulating vitamin C. Sensitivity analysis using 6 different analytical approaches yielded similar results. Moreover, our MR results were consistent with the null findings from the meta-analysis exploring prospective associations of dietary or supplemental vitamin C intakes with cancer risk, except that higher dietary vitamin C intake, but not vitamin C supplement, was associated with a lower risk of lung cancer (risk ratio: 0.84, 95% confidence interval 0.71 to 0.99).. These findings provide no evidence to support that physiological-level circulating vitamin C has a large effect on risk of the five most common cancers in European populations, but we cannot rule out very small effect sizes.

Topics: Ascorbic Acid; Breast Neoplasms; Female; Genome-Wide Association Study; Humans; Male; Mendelian Randomization Analysis; Polymorphism, Single Nucleotide; Prospective Studies; Risk Factors; Vitamin D

The most frequent cancer in women is breast cancer, which is a major cause of death. Currently, there are many pharmacological therapies that have made possible the cure and resolution of this tumor. However, these therapies are accompanied by numerous collateral effects that influence the quality of life (QoL) of the patients to varying degrees. For this reason, attention is turning to the use of complementary medicine to improve QoL. In particular, there are increased trials of intravenous injection of vitamin C at high doses to enhance the antitumor activity of drugs and/or decrease their side effects. This review intends to underline the anticancer mechanisms of vitamin C that could explain its efficacy for treating breast cancer, and why the use of vitamin C at high doses could help patients with breast cancer to enhance the efficacy of pharmacological therapies and/or decrease their side effects.

Topics: Animals; Antineoplastic Agents; Ascorbic Acid; Breast Neoplasms; Complementary Therapies; Female; Humans; Quality of Life

Vitamin C is implicated in various bodily functions due to its unique properties in redox homeostasis. Moreover, vitamin C also plays a great role in restoring the activity of 2-oxoglutarate and Fe

Topics: Ascorbic Acid; Basic Helix-Loop-Helix Transcription Factors; Brain Neoplasms; Breast Neoplasms; Carcinogenesis; Dehydroascorbic Acid; Dioxygenases; DNA Methylation; DNA-Binding Proteins; Epigenesis, Genetic; Female; Glioma; Glucose Transport Proteins, Facilitative; Hematologic Neoplasms; Homeostasis; Humans; Hypoxia-Inducible Factor 1; Ketoglutaric Acids; Male; Melanoma; Mixed Function Oxygenases; Neoplasms; Oxidation-Reduction; Polymorphism, Genetic; Prostatic Neoplasms; Proto-Oncogene Proteins; Sodium-Coupled Vitamin C Transporters; Vitamins

Latest data from International Agency for Cancer Research shows that breast cancer is the leading cancer site in women and is the leading cause of death among female cancers. Induction of reactive oxygen species (ROS) and oxidative stress as a consequence of impaired balance between prooxidants and antioxidants are suggested to be involved in induction and progression of breast cancer. Cancer cells are found to exhibit higher levels of ROS compared to normal cells. However increased antioxidant defence which balances the oxidative status within the cancer cells suggests that high ROS levels may prevent tumorigenesis via various mechanisms. These contradictory roles of ROS and oxidative stress in breast cancer let scientists investigate potential oxidative stress modulators as anticancer strategies.. In the present review we address the mechanisms of ROS production in breast cancer cells, the role of impaired oxidative status as well as the benefits of introducing oxidative stress modulators in therapeutic strategies in breast cancer. This review is focusing more on melatonin which we have been working on during the last decade. Our data, in accordance with the literature, suggest an important role for melatonin in breast cancer prevention and adjuvant therapy.

Topics: Animals; Ascorbic Acid; Breast Neoplasms; Carotenoids; Female; Humans; Melatonin; Oxidative Stress; Reactive Oxygen Species; Resveratrol; Stilbenes; Tocopherols

Plasma antioxidants are supposed to be directly related to breast cancer risk. However, the results remain inconsistent. Herein, we carried this meta-analysis to comprehensively summarize the associations between plasma retinol, vitamins A, C and α-tocopherol and breast cancer risk.. We searched PubMed, Embase and the Cochrane Databases (through September 24, 2014) and the reference lists of the retrieved articles in English with sufficient information to estimate relative risk or odds ratio and the 95% confidence intervals (CIs), or with mean serum/plasma level of vitamins and SD/SEM/p value in breast cancer and controls. Two reviewers independently extracted data using a standardized form, with any discrepancy adjudicated by the third reviewer.. Forty studies entered this meta-analysis. For the pooled OR, no significant association between plasma retinol and breast cancer was observed (p = 0.13). Significant association was observed between plasma α-tocopherol and breast cancer (pooled OR 0.42, 95% CI 0.25, 0.72, p = 0.00) in the subgroup with the median lowest level of 5.74-9.16 μmol/L. For the weighted mean difference (WMD), the plasma α-tocopherol and vitamin C level between breast cancer and controls were significantly different [WMD = -0.93 μmol/L (95% CI -1.26, -0.61, p = 0.00) and -2.51 μmol/L (95% CI -4.00, -1.02, p = 0.00), respectively]. No significant association between plasma retinol and vitamin A and breast cancer was observed.. Severe α-tocopherol deficiency could increase breast cancer risk. The association between plasma vitamin C and breast cancer was only significant in case-control studies. There was no significant association between other vitamins and breast cancer risk.

Topics: alpha-Tocopherol; Ascorbic Acid; Breast Neoplasms; Odds Ratio; Regression Analysis; Risk Factors; Vitamin A

The association between dietary vitamin C intake and breast cancer survival is inconsistent and few studies have specifically examined vitamin C supplement use among women with breast cancer. The purpose of this study was to summarise results from prospective studies on the association between vitamin C supplement use and dietary vitamin C intake and breast cancer-specific mortality and total mortality.. Studies were identified using the PubMed database through February 6, 2014 and by examining the references of retrieved articles. Prospective studies were included if they reported relative risks (RR) with 95% confidence intervals (95% CIs) for at least two categories or as a continuous exposure. Random-effects models were used to combine study-specific results.. The ten identified studies examined vitamin C supplement use (n=6) and dietary vitamin C intake (n=7) and included 17,696 breast cancer cases, 2791 total deaths, and 1558 breast cancer-specific deaths. The summary RR (95% CI) for post-diagnosis vitamin C supplement use was 0.81 (95% CI 0.72-0.91) for total mortality and 0.85 (95% CI 0.74-0.99) for breast cancer-specific mortality. The summary RR for a 100mg per day increase in dietary vitamin C intake was 0.73 (95% CI 0.59-0.89) for total mortality and 0.78 (95% CI 0.64-0.94) for breast cancer-specific mortality.. Results from this meta-analysis suggest that post-diagnosis vitamin C supplement use may be associated with a reduced risk of mortality. Dietary vitamin C intake was also statistically significantly associated with a reduced risk of total mortality and breast cancer-specific mortality.

Topics: Antioxidants; Ascorbic Acid; Breast Neoplasms; Diet; Dietary Supplements; Female; Humans; Prospective Studies; Survival Analysis; Vitamins

To comprehensively summarize the associations between retinol, vitamins A, C, and E and breast cancer, and quantitatively estimate their dose-response relationships.. We searched PubMed, Embase, and Cochrane databases (from January 1982 to 15 March 2011) and the references of the relevant articles in English with sufficient information to estimate relative risk or odds ratio and the 95% confidence intervals, and comparable categories of vitamins. Two reviewers independently extracted data using a standardized form, with any discrepancy adjudicated by the third reviewer.. Overall, 51 studies met the inclusion criteria. Comparing the highest with the lowest intake, total vitamin A intake reduced the breast cancer risk by 17% (pooled OR = 0.83, 95% CI: 0.78-0.88). Further subgroup analysis based on study design did not change the significant reduction. Although the dietary vitamin A, dietary vitamin E, and total vitamin E intake all reduced breast cancer risk significantly when data from all studies were pooled, the results became nonsignificant when data from cohort studies were pooled. The significant association between total retinol intake and breast cancer in all studies became nonsignificant in case-control studies but remain significant in cohort studies. No significant dose-response relationship was observed in the higher intake of these vitamins with reduced breast cancer risk.. Our results indicate that both the total intake of vitamin A and retinol could reduce breast cancer risk. However, associations between other vitamins and breast cancer seem to be limited.

Topics: Ascorbic Acid; Breast Neoplasms; Case-Control Studies; Cohort Studies; Dose-Response Relationship, Drug; Female; Humans; Odds Ratio; Regression Analysis; Risk Factors; Vitamin A; Vitamin E; Vitamins

This article presents an overview of the role of vitamins in the risk, prevention, and treatment of breast cancer, with emphasis on current evidence from English-language articles published since 1 August 2002 and indexed in MEDLINE.. Findings from epidemiologic studies that have evaluated vitamin A and carotenoids in relation to breast cancer risk have been inconclusive. The available data, especially from prospective studies, do not support an association between vitamins E and C and risk of breast cancer. Recent studies suggest that folate plays an important role in the prevention of breast cancer, particularly among women consuming alcohol. Limited data also support a potential role of vitamin D in the prevention of breast cancer.. High intake of folate or adequate circulating levels of folate may reduce the risk of breast cancer. Adequate folate levels may be particularly important for women who are at higher risk of breast cancer because of high alcohol consumption. The inverse association between vitamin D and risk of breast cancer needs to be evaluated in more studies.

Topics: Ascorbic Acid; Breast Neoplasms; Carotenoids; Female; Humans; Risk Factors; Vitamin A; Vitamin B 12; Vitamin B 6; Vitamin D; Vitamin E; Vitamins

Although vitamin deficiency is encountered infrequently in developed countries, inadequate intake of several vitamins is associated with chronic disease.. To review the clinically important vitamins with regard to their biological effects, food sources, deficiency syndromes, potential for toxicity, and relationship to chronic disease.. We searched MEDLINE for English-language articles about vitamins in relation to chronic diseases and their references published from 1966 through January 11, 2002.. We reviewed articles jointly for the most clinically important information, emphasizing randomized trials where available.. Our review of 9 vitamins showed that elderly people, vegans, alcohol-dependent individuals, and patients with malabsorption are at higher risk of inadequate intake or absorption of several vitamins. Excessive doses of vitamin A during early pregnancy and fat-soluble vitamins taken anytime may result in adverse outcomes. Inadequate folate status is associated with neural tube defect and some cancers. Folate and vitamins B(6) and B(12) are required for homocysteine metabolism and are associated with coronary heart disease risk. Vitamin E and lycopene may decrease the risk of prostate cancer. Vitamin D is associated with decreased occurrence of fractures when taken with calcium.. Some groups of patients are at higher risk for vitamin deficiency and suboptimal vitamin status. Many physicians may be unaware of common food sources of vitamins or unsure which vitamins they should recommend for their patients. Vitamin excess is possible with supplementation, particularly for fat-soluble vitamins. Inadequate intake of several vitamins has been linked to chronic diseases, including coronary heart disease, cancer, and osteoporosis

Topics: Ascorbic Acid; Avitaminosis; Blood Coagulation; Breast Neoplasms; Carotenoids; Chronic Disease; Colorectal Neoplasms; Coronary Disease; Dietary Supplements; Female; Folic Acid; Fractures, Bone; Humans; Lung Neoplasms; Male; Neoplasms; Neural Tube Defects; Prostatic Neoplasms; Risk Factors; Vitamin A; Vitamin B 12; Vitamin B 6; Vitamin D; Vitamin E; Vitamin K; Vitamins

This review is a summary of three reference books and of the final report of a European concerted action. The data have been updated by an analysis of recent publications, according to the same methodological criteria as those used in the reference books: sample size, quality of questionnaire and statistical methods. Mechanistic hypothesis are considered for each microcompounds, the effect of which is situated along the natural history of cancer. Few studies have considered folates effect on breast cancer, and they observed an interaction with the risk related to alcohol consumption, which is decreased with a high intake of folates. Many studies considered the effect of vitamin C and E, and carotenoids, but results are inconsistent. Conflicting results were also observed in studies on fibre and breast cancer. However, although only half of the studies showed a protective effect, the strength of the biological mechanisms give support to the hypothesis of a protection provided by fibre. The situation is comparable with phyto-estrogens: epidemiological studies are scarce and few of them show significant protection, but several plausible biological mechanisms are proposed, either related to the negative modulation of estrogen receptor by phyto-estrogen, or to the inhibition of proliferation by action on various enzymes. At the present time, caution in the interpretation of the results and in the use of plant microcompounds in prevention or therapy is strongly recommended.

Topics: Antioxidants; Ascorbic Acid; Breast Neoplasms; Diet; Dietary Fiber; Estrogens, Non-Steroidal; Female; Humans; Isoflavones; Phytoestrogens; Plant Preparations; Vegetables; Vitamin E

A meta-analysis was carried out, in order to summarise published data on the relationship between breast cancer, fruit and vegetable consumption and/or the intake of beta-carotene and vitamin C. Relative risks were extracted from 26 published studies from 1982 to 1997. Random and fixed effects models were used. Between studies, heterogeneity was found for vegetables, fruit, vitamin C but not for beta-carotene. Summary relative risk (RR) estimates based upon a random effects model, except for beta-carotene, for 'high consumption' compared with 'low consumption', derived from the studies satisfying the inclusion criteria were as follows: vegetable consumption: RR=0.75 (95% CI (confidence interval) 0.66-0.85) from 17 studies; fruit consumption: RR=0.94 (95% CI 0.79-1.11) from 12 studies; vitamin C: RR=0.80 (95% CI 0.68-0.95) from 9 studies; beta-carotene: RR=0.82 (95% CI 0.76-0.91) from 11 studies. This analysis confirms the association between intake of vegetables and, to a lesser extent, fruits and breast cancer risk from published sources. Increasing vegetable consumption might reduce the risk of breast cancer.

Topics: Ascorbic Acid; beta Carotene; Breast Neoplasms; Case-Control Studies; Cohort Studies; Diet; Female; Fruit; Humans; Odds Ratio; Risk Factors; Vegetables

Topics: Adult; Aged; Ascorbic Acid; Breast Neoplasms; Carbohydrates; Case-Control Studies; Diet; Dietary Fats; Dietary Proteins; Female; Humans; Indonesia; Middle Aged; Nutritional Status; Risk; Vitamin A

The potential for a reduction in dietary fat or for an increase in dietary fiber to reduce breast cancer risk has been debated for some years. It is argued here that available research data, even though extensive, leave open hypotheses ranging from little or no potential to major public health potential for breast cancer prevention by means of these dietary maneuvers. Some elements of a research strategy for testing these and other dietary breast cancer prevention hypotheses are described.

Topics: Adult; Aged; Animals; Anticarcinogenic Agents; Ascorbic Acid; Asia; Asian; beta Carotene; Breast Neoplasms; Case-Control Studies; Cohort Studies; Dietary Fats; Dietary Fiber; Estrogens; Feeding Behavior; Female; Forecasting; Humans; Mammary Neoplasms, Experimental; Meta-Analysis as Topic; Mice; Middle Aged; Models, Biological

A large part of the epidemiological debate on diet and breast cancer has been dominated by the issue of whether fat, particularly animal fat, increases risk. Lately, the possible protective effect of various dietary constituents has received more attention. Vitamins C and E, and beta-carotene have antioxidant activity and may thus provide a cellular defence against reactive oxygen species that damage DNA. Dietary fibre may influence oestrogen metabolism. A large case-control study (2,569 breast cancer and 2,588 hospital controls) conducted in six Italian areas between 1991 and 1994 suggested that a diet rich in several micronutrients was associated with significantly lowered risk. After allowance for non-dietary risk correlates, energy intake and the mutual confounding effect of the various micronutrients, beta-carotene, vitamin E and calcium were associated with odds ratios in the highest intake quintile compared to the lowest one of 0.84, 0.75 and 0.81, respectively. Among different types of fibre, only cellulose intake showed a moderate inverse association. Evidence from other studies suggests that a favourable role of some micronutrients is possible, albeit probably less important than for cancers of the stomach and colon-rectum. Indeed, the relationship between fruit and vegetable intake is also less marked/consistent for breast cancer than for other sites. Among agents that have only recently been investigated, isoflavones, which are weak oestrogens, are of particular interest.

Topics: Ascorbic Acid; Breast Neoplasms; Case-Control Studies; Dietary Fiber; Female; Fruit; Humans; Micronutrients; Odds Ratio; Prospective Studies; Vegetables; Vitamin A; Vitamin E

Topics: Adult; Aged; Ascorbic Acid; beta Carotene; Breast Neoplasms; Case-Control Studies; Cohort Studies; Colonic Neoplasms; Diet; Dietary Fats; Ethanol; Female; Fruit; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasms; Prospective Studies; Rectal Neoplasms; Risk Factors; Smoking; Stomach Neoplasms; Vegetables; Vitamin E

We reviewed epidemiologic evidence on the relationship between four antioxidant micronutrients (vitamin A, vitamin C, vitamin E, and selenium) and breast cancer risk. Available data support a modest protective effect of vitamin A, although more studies are needed to examine further this association and to assess the relative contributions of preformed vitamin A (retinol) and carotenoids. In addition, the possibility that some other component of vitamin A-rich foods may account for this observed association should be explored. Data on the relationship between vitamins C and E and breast cancer risk are limited and inconsistent, and further information is necessary. A substantial body of evidence indicates a lack of any appreciable effect of selenium intake on breast cancer risk, at least within the range of human diets. Future observational studies should ideally be prospective in design, as prospective studies are less prone to selection and recall bias than are case-control studies, and should address methodologic issues such as confounding by other micronutrients and appropriate storage conditions of blood specimens. Although hypotheses relating micronutrient intake to risk of breast cancer should be tested in randomized trials, ethical and logistical constraints make these studies difficult to perform.

Topics: Antioxidants; Ascorbic Acid; Breast Neoplasms; Diet; Female; Humans; Risk Factors; Selenium; Vitamin A; Vitamin E; Vitamins

Evidence pertaining to the role of dietary factors in carcinogenesis comes from both epidemiological studies and laboratory experiments. In 1982, the Committee on Diet, Nutrition, and Cancer of the National Research Council conducted a comprehensive evaluation of this evidence. That assessment as well as recent epidemiological and laboratory investigations suggest that a high fat diet is associated with increased susceptibility to cancer of different sites, particularly the breast and colon, and to a lesser extent, the prostate. Current data permit no definitive conclusions about other dietary macroconstituents including cholesterol, total caloric intake, protein, carbohydrates and total dietary fiber. Specific components of fiber, however, may have a protective effect against colon cancer. In epidemiological studies, frequent consumption of certain fruits and vegetables, especially citrus fruits and carotene-rich and cruciferous vegetables, is associated with a lower incidence of cancers at various sites. The specific components responsible for these effects are not clearly identified, although the epidemiological evidence appears to be most consistent for a protective effect of carotene on lung cancer and less so for vitamins A and C and various cancer sites. The laboratory evidence is most consistent for vitamin A deficiency and enhanced tumorigenesis, and for the ability of various nonnutritive components in cruciferous vegetables to block in-vivo carcinogenesis. The data for minerals and carcinogenesis are extremely limited, although preliminary evidence from both epidemiological and laboratory studies suggests that selenium may protect against overall cancer risk. Frequent consumption of cured, pickled, or smoked foods, possibly because they may contain nitrosamines or polycyclic aromatic hydrocarbons, appears to increase the risk of esophageal or stomach cancer, however, the specific causative agents in these foods are not clearly identified. Excessive alcohol consumption among smokers appears to be associated with an elevated risk of cancers of the oral cavity, esophagus, larynx, and respiratory tract. The mechanisms of action of dietary factors on carcinogenesis are poorly understood. The NRC committee, and more recently, the National Cancer Institute and the American Cancer Society have proposed interim dietary guidelines to lower the risk of cancer. These guidelines are consistent with general dietary recommendations proposed by U.S. government

Topics: Animals; Ascorbic Acid; Breast Neoplasms; Calcium; Carcinogens; Cholesterol; Colonic Neoplasms; Diet; Dietary Carbohydrates; Dietary Fats; Dietary Fiber; Dietary Proteins; Energy Intake; Environmental Pollutants; Ethanol; Food; Forecasting; Humans; Iron; Minerals; Mutagens; Neoplasms; Nutritional Physiological Phenomena; Research; Retinoids; Risk; Selenium; Vitamin D; Vitamin E; Vitamins; Zinc

Topics: Animals; Animals, Laboratory; Ascorbic Acid; Breast Neoplasms; Carcinogens; Colonic Neoplasms; Diet; Dietary Carbohydrates; Dietary Fats; Dietary Proteins; Energy Intake; Female; Humans; Male; Mammary Neoplasms, Experimental; Mice; Neoplasms; Neoplasms, Experimental; Rats; Selenium; Vitamin A

The relationship of vitamins to cancer is very complex. Three types of interactions are possible: the effect of vitamins on tumor growth, the effect of tumors on vitamin metabolism, and the effect of vitamins on chemical carcinogens and anti-tumor chemotherapeutic agents. The significance of vitamins with particular references to vitamins A,B-complex and C, in cancer has been reviewed.

Topics: Antineoplastic Agents; Ascorbic Acid; Bone Neoplasms; Brain Neoplasms; Breast Neoplasms; Bronchial Neoplasms; Humans; Neoplasms; Nutritional Physiological Phenomena; Tryptophan; Vitamin A; Vitamin B Complex; Vitamin B Deficiency; Vitamins

Topics: Adrenal Glands; Ascorbic Acid; Breast Neoplasms; Calciphylaxis; Calcium; Growth Hormone; Humans; Osteogenesis; Osteomalacia; Osteoporosis; Parathyroid Glands; Phosphates; Retinoids; Vitamin A; Vitamin D; Vitamin E; Vitamin K; Vitamins

Reactive oxygen/nitrogen species generated by antineoplastic agents are prime suspects for the toxic side-effects of acute or chronic chemotherapy. The present study was undertaken to test whether vitamins C and E (VCE) supplementation protect against some of the harmful effects of commonly used anticancer drugs in breast-cancer patients.. In a randomized 5-month study, the activity of various antioxidant enzymes (superoxide dismutase, catalase, glutathione-S-transferase and glutathione reductase) and the levels of malondialdehyde and reduced glutathione were measured in forty untreated breast-cancer patients (stage II) and compared with those of healthy controls. The degree of DNA damage was also assessed in the peripheral lymphocytes of the patients by alkaline single cell gel electrophoresis. The untreated patients were then randomly assigned to either treatment with chemotherapy alone (5-fluorouracil 500 mg/m(2) i.v. day 1, doxorubicin 50 mg/m(2) i.v. day 1 and cyclophosphamide 500 mg/m(2) i.v. day 1, every 3 weeks for six cycles) or to the same chemotherapy regimen supplemented with VCE (vitamin C 500 mg tablet and vitamin E 400 mg gelatin capsule). On completion of the treatments, both the groups were studied again for the levels of the markers measured prior to treatment.. The untreated group showed significantly lower levels of antioxidant enzymes (P < 0·001) and reduced glutathione (P < 0·001), and more extensive lipid peroxidation (P < 0·001) and DNA damage than healthy controls. Similar but less pronounced patterns were observed in the patients receiving chemotherapy alone. The group of patients receiving VCE supplementation had all the marker levels moving towards normal values. Activities of superoxide dismutase, catalase, glutathione-S-transferase and glutathione reductase, and the levels of reduced glutathione were significantly increased (P < 0·01) while, the levels of malondialdehyde and DNA damage were significantly (P < 0·01) reduced in the VCE supplemented group relative to those of patients receiving chemotherapy alone as well as relative to the pretreatment levels.. Co-administration of VCE restored antioxidant status, lowered by the presence of breast-cancer and chemotherapy. DNA damage was also reduced by VCE. The results suggest that VCE should be useful in protecting against chemotherapy-related side-effects and a randomized control trial to evaluate the effectiveness of VCE in breast-cancer patients using clinical outcomes would be appropriate.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Antioxidants; Ascorbic Acid; Breast Neoplasms; Case-Control Studies; Comet Assay; Cyclophosphamide; DNA Damage; Doxorubicin; Female; Fluorouracil; Humans; Middle Aged; Neoplasm Staging; Prospective Studies; Vitamin E

Higher plasma micronutrient levels have been associated with decreased cancer risks. The objective of this study was to determine the relative effects of reduced fat and/or increased fruit-vegetable (FV) intakes on plasma micronutrient levels.. Healthy, premenopausal women with a family history of breast cancer (n = 122) were randomized across four diet arms for one year in a 2 x 2 factorial design study: control, low-fat, high fruit-vegetable and combination low-fat/high FV diets. Levels of plasma micronutrients were measured in plasma at 0, 3, 6 and 12 months.. The high FV intervention, regardless of fat intake, significantly increased alpha-carotene, beta-carotene and vitamin C levels in plasma. Only the combination high FV, low-fat intervention significantly increased plasma beta-cryptoxanthin and zeaxanthin levels over time. Although alpha-tocopherol was not affected, a potential concern is that the low-fat intervention resulted in significantly decreased both gamma-tocopherol dietary intakes and plasma levels, regardless of whether or not FV intakes were concomitantly increased.. Unlike alpha-tocopherol, gamma-tocopherol plasma levels were decreased by a low fat diet, perhaps because gamma-tocopherol is not generally added to foods nor widely used in vitamin E supplements. The decreased dietary intakes and plasma levels of gamma-tocopherol with a low-fat diet may have implications for health risks since the biological functions of the different tocopherol isomers have been reported to be distinct.

Topics: Adult; alpha-Tocopherol; Antioxidants; Area Under Curve; Ascorbic Acid; Breast Neoplasms; Carotenoids; Diet, Fat-Restricted; Dietary Fats; Female; Fruit; gamma-Tocopherol; Humans; Micronutrients; Middle Aged; Risk Factors; Vegetables

Although alcohol intake has been positively associated with breast cancer risk in epidemiologic studies, the mechanisms mediating this association are speculative.. The Postmenopausal Women's Alcohol Study was designed to explore the effects of moderate alcohol consumption on potential risk factors for breast cancer. In the present analysis, we evaluated the relationship of alcohol consumption with antioxidant nutrients and a biomarker of oxidative stress.. Participants (n=53) consumed a controlled diet plus each of three treatments (15 or 30 g alcohol/day or a no-alcohol placebo beverage), during three 8-week periods in random order. We measured the antioxidants, vitamin E (alpha (alpha)- and gamma (gamma)-tocopherols), selenium, and vitamin C in fasting blood samples which were collected at the end of diet periods, treated and frozen for assay at the end of the study. We also measured 15-F(2t)-IsoP isoprostane, produced by lipid peroxidation, which serves as an indicator of oxidative stress and may serve as a biomarker for conditions favorable to carcinogenesis.. After adjusting for BMI (all models) and total serum cholesterol (tocopherol and isoprostane models) we observed a significant 4.6% decrease (P=0.02) in alpha-tocopherol and a marginally significant 4.9% increase (P=0.07) in isoprostane levels when women consumed 30 g alcohol/day (P=0.06 and 0.05 for overall effect of alcohol on alpha-tocopherol and isoprostanes, respectively). The other antioxidants were not significantly modified by the alcohol treatment.. These results suggest that moderate alcohol consumption increases some biomarkers of oxidative stress in postmenopausal women.

Topics: Alcohol Drinking; Antioxidants; Ascorbic Acid; Biomarkers; Breast Neoplasms; Cross-Over Studies; Ethanol; Female; Humans; Isoprostanes; Lipid Peroxidation; Middle Aged; Oxidative Stress; Postmenopause; Risk Factors; Selenium; Vitamin E

A randomized double blind placebo-controlled trial of efficiency of a dietary supplement "Karinat" in patients with benign breast disease was carried out. Karinat contains beta-carotene 2.5 mg, alpha-tocopherol 5 mg, ascorbic acid 30 mg and garlic powder 150 mg per one tablet. Out of 66 patients, 33 patients were given karinat, 33 were given placebo. The patients reccived a tablet of karinal or placebo twice a day during 6 months. Examinations of the patients included clinical estimation of symptoms of mastopathy and dysalgomenorrhea, breast sonography and mammography. It was found that karinat reduced the severity of mastalgia, premenstrual syndrome, dysmenorrhea and algomenorrhea and caused regression of palpable symptoms of the breast fibromatosis. On the whole karinat had positive action in 75.8% that was significantly greater by 45.5% as compared with placebo. Karinat may be useful for the treatment of patients with benign breast disease.

Topics: Adult; alpha-Tocopherol; Antioxidants; Ascorbic Acid; beta Carotene; Breast Diseases; Breast Neoplasms; Data Interpretation, Statistical; Dietary Supplements; Double-Blind Method; Dysmenorrhea; Female; Fibroadenoma; Humans; Mammography; Palpation; Placebos; Premenstrual Syndrome; Time Factors; Treatment Outcome; Ultrasonography, Mammary

Tamoxifen, a non-steroidal antiestrogen, has been used in the hormonal treatment for breast cancer. The hepatic estrogenic effect of tamoxifen causes severe triglyceridemia. The combined effect of tamoxifen, vitamin C and vitamin E on plasma lipid and lipoprotein is important, since, vitamin C and vitamin E encumbered the lipid abnormalities instigated by tamoxifen. Therefore supplementation of vitamin C (Celin 500 mg) and vitamin E (Evion 400 mg) for 90 days along with tamoxifen (10 mg twice a day) to postmenopausal breast cancer patients was ventured. In tamoxifen-treated patients, total cholesterol (TC), free cholesterol (FC), phospholipids (PL), free fatty acids (FFA), low density lipoprotein cholesterol (LDL) levels were decreased and the triglycerides (TG), ester cholesterol (EC), high density lipoprotein cholesterol (HDL) and very low density lipoprotein cholesterol (VLDL) levels were increased. Combination therapy reduce all the cholesterol level and VLDL, LDL. TG levels were significantly decreased and HDL, EC levels were significantly increased. These results suggested that tamoxifen treatment is the most effective during co-administration of vitamin C and vitamin E in that they reduce the tamoxifen-induced hypertriglyceridemia.

Topics: Antineoplastic Agents, Hormonal; Ascorbic Acid; Breast Neoplasms; Cholesterol; Cholesterol Esters; Cholesterol, HDL; Cholesterol, LDL; Cholesterol, VLDL; Fatty Acids, Nonesterified; Female; Humans; Lipids; Lipoproteins; Middle Aged; Phospholipids; Tamoxifen; Triglycerides; Vitamin E

Thirty-two typical patients with breast cancer, aged 32-81 years and classified 'high risk' because of tumor spread to the lymph nodes in the axilla, were studied for 18 months following an Adjuvant Nutritional Intervention in Cancer protocol (ANICA protocol). The nutritional protocol was added to the surgical and therapeutic treatment of breast cancer, as required by regulations in Denmark. The added treatment was a combination of nutritional antioxidants (Vitamin C: 2850 mg, Vitamin E: 2500 iu, beta-carotene 32.5 iu, selenium 387 micrograms plus secondary vitamins and minerals), essential fatty acids (1.2 g gamma linolenic acid and 3.5 g n-3 fatty acids) and Coenzyme Q10 (90 mg per day). The ANICA protocol is based on the concept of testing the synergistic effect of those categories of nutritional supplements, including vitamin Q10, previously having shown deficiency and/or therapeutic value as single elements in diverse forms of cancer, as cancer may be synergistically related to diverse biochemical dysfunctions and vitamin deficiencies. Biochemical markers, clinical condition, tumor spread, quality of life parameters and survival were followed during the trial. Compliance was excellent. The main observations were: (1) none of the patients died during the study period. (the expected number was four.) (2) none of the patients showed signs of further distant metastases. (3) quality of life was improved (no weight loss, reduced use of pain killers). (4) six patients showed apparent partial remission.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Antioxidants; Ascorbic Acid; beta Carotene; Biomarkers; Breast Neoplasms; Carotenoids; Chemotherapy, Adjuvant; Coenzymes; Combined Modality Therapy; Fatty Acids, Essential; Female; Follow-Up Studies; Humans; Lymphatic Metastasis; Mastectomy; Middle Aged; Neoplasm Metastasis; Quality of Life; Remission Induction; Risk; Selenium; Treatment Outcome; Ubiquinone; Vitamin E

We aimed to examine whether anthropometric indices, dietary factors, and nutrient intakes of women with and without breast cancer (BrCa) are associated with the oxidative balance score (OBS). This case-control study was carried out among 253 patients with BrCa and 267 healthy subjects aged >18 years. The OBS was calculated by using the following 13 dietary and non-dietary anti- and prooxidant components: dietary antioxidants (selenium, fiber, β-carotene, vitamin D, vitamin C, vitamin E, and folate), dietary prooxidants (iron and saturated and polyunsaturated fatty acids), and nondietary anti- (physical activity) and prooxidants (smoking and obesity). The binary logistic regression was used to determine the association OBS with BrCa. After adjusting for potential confounders in the final model, there was evidence that the odds of BrCa decreased with increasing categories of the OBS (OR = 0.53, 95% CI 0.28 - 0.98; P-trend = 0.021). When we made stratified analysis by menopausal status, OBS was inversely associated with odds of BrCa in premenopausal women after adjusting for potential confounders. No significant association was found between OBS and odds of BrCa among post-menopausal women. Our data suggest that OBS scores were associated with decreased BrCa risk in the overall population.

Topics: Antioxidants; Ascorbic Acid; Breast Neoplasms; Case-Control Studies; Diet; Female; Humans; Risk Factors

Recent observational studies and meta-analyses have shown that vitamin C reduces cancer incidence and mortality, but the underlying mechanisms remain unclear. We conducted a comprehensive pan-cancer analysis and biological validation in clinical samples and animal tumor xenografts to understand its prognostic value and association with immune characteristics in various cancers.. We used the Cancer Genome Atlas gene expression data involving 5769 patients and 20 cancer types. Vitamin C index (VCI) was calculated using the expression of 11 genes known to genetically predict vitamin C levels, which were classified into high and low subgroups. The correlation between VCI and patient overall survival (OS), tumor mutational burden (TMB), microsatellite instability (MSI), and immune microenvironment was evaluated, using Kaplan-Meier analysis method and ESTIMATE (https://bioinformatics.mdanderson.org/estimate/). Clinical samples of breast cancer and normal tissues were used to validate the expression of VCI-related genes, and animal experiments were conducted to test the impact of vitamin C on colon cancer growth and immune cell infiltration.. Significant changes in expression of VCI-predicted genes were observed in multiple cancer types, especially in breast cancer. There was a correlation of VCI with prognosis in all samples (adjusted hazard ratio [AHR] = 0.87; 95% confidence interval [CI] = 0.78-0.98;. VCI is significantly correlated with OS and immunotypes in multiple cancers, and vitamin C might have therapeutic potential in colon cancer.

Topics: Animals; Ascorbic Acid; Breast Neoplasms; Carcinoma, Renal Cell; Colonic Neoplasms; Female; Humans; Kidney Neoplasms; Lung Neoplasms; Mice; Rectal Neoplasms; Tumor Microenvironment; Vitamins

Dietary antioxidant capacity (dTAC) and dietary inflammatory index (DII) are commonly used to assess nutrition. This prospective study examined dTAC, DII, and serum biomarkers in women with breast cancer (BC). Patients were followed-up before surgery (T

Topics: Antioxidants; Ascorbic Acid; Biomarkers; Breast Neoplasms; Diet; Female; Humans; Prospective Studies; Vitamins

Some previous studies suggested that high supplemental vitamin C intake may be associated with an increased risk of breast cancer, although evidence is inconsistent.. Our objective was to study the association between vitamin C intake and breast cancer risks using regularly updated assessments of intake over a long follow-up.. We prospectively followed 88,041 women aged 33 to 60 years from the Nurses' Health Study (1980-2014) and 93,372 women aged 26 to 45 years from the Nurses' Health Study II (1991-2013). A total of 11,258 incident invasive breast cancers among 181,413 women were diagnosed. Data on vitamin C intake were collected every 2-4 years via a validated FFQ and specific questions on dietary supplement use. Multivariate HRs and 95% CIs for incident invasive breast cancer were estimated with Cox models.. During follow-up, 82% of participants ever used supplements containing vitamin C, including multivitamins. Cumulative total vitamin C intake (HR for quintiles 5 compared with 1 = 0.97; 95% CI: 0.91-1.03; Ptrend = 0.81), dietary vitamin C intake (HR for quintiles 5 compared with 1 = 0.98; 95% CI: 0.92-1.04; Ptrend = 0.57), and supplemental vitamin C intake (HR for quintiles 5 compared with 1 in users = 1.02; 95% CI: 0.94-1.09; Ptrend = 0.77) were not associated with breast cancer risks. Results were unchanged when different exposure latencies were considered. The results did not differ by menopausal status, postmenopausal hormone therapy use, or BMI. No differences were observed by estrogen receptor status of the tumor.. Our results do not support any important association between total, dietary, or supplemental vitamin C intake and breast cancer risks.

Topics: Ascorbic Acid; Breast Neoplasms; Dietary Supplements; Female; Humans; Male; Nurses; Prospective Studies; Risk Factors; Vitamins

Vitamin C may impact the efficiency of radiation therapy (RT) in breast cancer. The effects of RT alone or in combination with vitamin C in SKBR3, MDA-MB-231, and MCF7 cells were compared using clonogenic assay, proliferation assay (MTT), cell cycle analysis, and Western blot. Vitamin C use was assessed in 1803 breast cancer patients 2002-2017 in relation to clinicopathological features and recurrences after RT. Vitamin C combined with RT resulted in non-significant increases in colony formation and minor differences in cell cycle arrest and expression of studied proteins, compared to RT alone. Lower vitamin C doses alone or in combination with RT, resulted in higher proliferation with MTT than higher vitamin C doses in a cell line-dependent manner. Vitamin C use was associated with lower histological grade and BMI but not recurrence risk in RT-treated patients (LogRank

Topics: Ascorbic Acid; Breast Neoplasms; Cell Line, Tumor; Cell Proliferation; Female; Humans; MCF-7 Cells; Radiation Tolerance; Vitamins

The main focus of our study is to assess the anti-cancer activity of cimetidine and vitamin C via combating the tumor supportive role of mast cell mediators (histamine, VEGF, and TNF-α) within the tumor microenvironment and their effect on the protein kinase A(PKA)/insulin receptor substrate-1(IRS-1)/phosphatidylinositol-3-kinase (PI3K)/serine/threonine kinase-1 (AKT)/mammalian target of rapamycin (mTOR) cue in Ehrlich induced breast cancer in mice. In vitro study was carried out to evaluate the anti-proliferative activity and combination index (CI) of the combined drugs. Moreover, the Ehrlich model was induced in mice via subcutaneous injection of Ehrlich ascites carcinoma cells (EAC) in the mammary fat pad, and then they were left for 9 days to develop obvious solid breast tumor. The combination therapy possessed the best anti-proliferative effect, and a CI < 1 in the MCF7 cell line indicates a synergistic type of drug interaction. Regarding the in vivo study, the combination abated the elevation in the tumor volume, and serum tumor marker carcinoembryonic antigen (CEA) level. The serum vascular endothelial growth factor (VEGF) level and immunohistochemical staining for CD34 as markers of angiogenesis were mitigated. Additionally, it reverted the state of oxidative stress and inflammation. Meanwhile, it caused an increment in apoptosis, which prevents tumor survival. Furthermore, it tackled the elevated histamine and cyclic adenosine monophosphate (cAMP) levels, preventing the activation of the (PKA/IRS-1/PI3K/AKT/mTOR) cue. Finally, we concluded that the synergistic combination provided a promising anti-neoplastic effect via reducing the angiogenesis, oxidative stress, increasing apoptosis,as well as inhibiting the activation of PI3K/AKT/mTOR cue, and suggesting its use as a treatment option for breast cancer.

Topics: Animals; Apoptosis; Ascorbic Acid; Breast Neoplasms; Cell Line, Tumor; Cell Proliferation; Cimetidine; Female; Histamine; Mice; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Signal Transduction; TOR Serine-Threonine Kinases; Tumor Microenvironment; Vascular Endothelial Growth Factor A

Biosynthesis of gold nanoparticles (AuNPs) using algal polysaccharides is a simple, low-cost, and an eco-friendly approach. In the current study, different concentrations of Arthospira platensis exopolysaccharides (EPS) were used to synthetize AuNPs via the reduction of gold ions. The biologically synthesized AuNPs (AuNPs1, AuNPs2, AuNPs3) were prepared in 3 different forms through the utilization of three different ratios of EPS-reducing agents. AuNPs analysis confirmed the spherical shape of the EPS-coated AuNPs. Furthermore, AuNPs prepared by EPS and L-ascorbic acid (AuNPs3) showed more stability than the AuNPs colloidal solution that was prepared using only L-ascorbic acid. Analysis of the antimicrobial effects of AuNPs showed that E. coli was the most sensitive bacterial species for AuNPs3 and AuNPs1 with inhibition percentages of 88.92 and 83.13%, respectively. Also, safety assay results revealed that AuNPs3 was the safest biogenic AuNPs for the tested noncancerous cell line. The anticancer assays of the biogenic AuNPs1, AuNPs2, and AuNPs3 against MCF-7 cell line indicated that this cell line was the most sensitive cell line to all treatments and it showed inhibition percentages of 66.2%, 57.3%, and 70.2% to the three tested AuNPs, respectively. The AuNPs also showed abilities to arrest MCF-7 cells in the S phase (77.34%) and increased the cellular population in the sub G0 phase. Gene expression analysis showed that AuNPs3 down regulated Bcl2, Ikapα, and Survivn genes in MCF-7 treated-cells. Also, transmission electron microscopy (TEM) analysis of MCf-7 cells revealed that AuNPs 3 and AuNPs2 were localized in cell vacuoles, cytoplasm, and perinuclear region.

Topics: Anti-Bacterial Agents; Ascorbic Acid; Breast Neoplasms; Escherichia coli; Female; Gold; Green Chemistry Technology; Humans; Metal Nanoparticles; Microbial Sensitivity Tests; Plant Extracts

This study investigated the association between micronutrient intake and breast cancer risk in South Korean adult women. This association was stratified according to body mass index (BMI) categories. Data from the Korean Genome and Epidemiology Study (KoGES) and the Health Examinee Study were analyzed. Altogether, 63,337 individuals (aged ≥40 years) completed the baseline and first follow-up surveys; 40,432 women without a history of cancer at baseline were included in this study. The association between micronutrient intake and breast cancer was determined by estimating the hazard ratio (HR) and 95% confidence interval (CI) using the Cox proportional hazard regression model. A stratified analysis by BMI (<25 kg/m2 and ≥25 kg/m2) was performed. The an analysis of 15 micronutrients and breast cancer risk revealed that none of the micronutrients were associated with breast cancer risk after adjusting for covariates. In obese women, the risk of breast cancer was significantly reduced in the group that consumed vitamin C more than the recommended level (HR = 0.54, 95% CI: 0.31−0.93) and vitamin B6 levels above the recommended level (HR = 0.48, 95% CI: 0.25−0.89). In obese women, exceeding the recommended daily intake levels of vitamin C and vitamin B6 was associated with a lower risk of breast cancer. However, other micronutrients were not associated with breast cancer risk in these women.

Topics: Adult; Ascorbic Acid; Body Mass Index; Breast Neoplasms; Cohort Studies; Eating; Female; Humans; Micronutrients; Obesity; Republic of Korea; Risk Factors; Vitamin B 6

Vitamin C (VC), in regard to its effectiveness against tumors, has had a controversial history in cancer treatment. However, the anticancer mechanisms of VC are not fully understood. Here, we reported that VC exerted an anticancer effect on cancer cell and xenograft models via inhibiting HIF-1α-dependent cell proliferation and promoting p53-dependent cell apoptosis. To be specific, VC modulated the competitive binding of HIF-1α and p53 to their common E3 ubiquitin ligase CBL, thereby inhibiting tumorigenesis. Moreover, VC treatment activated SIRT1, resulting in p53 deacetylation and CBL-p53 complex dissociation, which in turn facilitated CBL recruitment of HIF-1α for ubiquitination in a proteasome-dependent manner. Altogether, our results provided a mechanistic rationale for exploring the therapeutic use of VC in cancer therapy.

Topics: Ascorbic Acid; Binding, Competitive; Breast Neoplasms; Cell Line, Tumor; Female; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Proteasome Endopeptidase Complex; Sirtuin 1; Tumor Suppressor Protein p53; Ubiquitin; Ubiquitin-Protein Ligases

Topics: Animals; Ascorbic Acid; Breast Neoplasms; Cell Survival; Energy Metabolism; Female; Humans; Oxidation-Reduction; Oxidative Stress

Topics: Ascorbic Acid; Breast Neoplasms; Female; Humans; Oxidation-Reduction

Many studies have demonstrated that the extracellular domain of human epidermal growth factor receptor 2 (HER2 ECD) level in serum can act as a breast cancer biomarker and serve as a monitoring neoadjuvant therapy of breast cancer. In this study, we developed a sensitive ascorbic acid (AA)-mediated AuNBPs (gold nanobipyramids) growth method with NADH (reduced nicotinamide adenine dinucleotide I) assistance, and we further fabricated a high-resolution multicolor immunosensor for sensitive visual detection of HER2 ECD in serum by using AuNBPs as signal and antibody as recognition probe. The NADH-assisted AA-mediated method effectively suppressed color formation in the blank and greatly improved the sensitivity of mediating AuNBPs growth, allowing us to use a low concentration of AA to mediate AuNBPs growth to generate more colorful and clearer color changes. The proposed multicolor immunosensor has higher resolution and more color changes corresponding to HER2 ECD concentrations. It can be used to detect as low as 0.5 ng/mL of HER2 ECD by bare eye observation and 0.05 ng/mL of HER2 ECD by UV-visible spectrophotometry. Using the immunosensor, we have successfully detected HER2 ECD in human serum with a recovery of 94%-96% and an RSD (

Topics: Ascorbic Acid; Biomarkers, Tumor; Biosensing Techniques; Breast Neoplasms; Fluorescent Dyes; Gold; Humans; Immunoassay; Metal Nanoparticles; Molecular Structure; NAD; Particle Size; Receptor, ErbB-2; Surface Properties

Vitamin C (ascorbate) acts as an antioxidant and enzyme cofactor, and plays a vital role in human health. Vitamin C status can be affected by illness, with low levels being associated with disease due to accelerated turnover. However, robust data on the ascorbate status of patients with cancer are sparse. This study aimed to accurately measure ascorbate concentrations in plasma from patients with cancer, and determine associations with patient or tumor characteristics. We recruited 150 fasting patients with cancer (of 199 total recruited) from two cohorts, either prior to cancer surgery or during cancer chemo- or immunotherapy. A significant number of patients with cancer had inadequate plasma ascorbate concentrations. Low plasma status was more prevalent in patients undergoing cancer therapy. Ascorbate status was higher in women than in men, and exercising patients had higher levels than sedentary patients. Our study may prompt increased vigilance of ascorbate status in cancer patients.

Topics: Adult; Aged; Antioxidants; Ascorbic Acid; Ascorbic Acid Deficiency; Breast Neoplasms; Colonic Neoplasms; Exercise; Female; Health Surveys; Humans; Male; Middle Aged; Neoplasms; Nutritional Status; Risk Factors; Sedentary Behavior; Vitamins

Nineteen organoselenides were synthesized and tested for their intrinsic cytotoxicity in hepatocellular carcinoma (HepG2) and breast adenocarcinoma (MCF-7) cell lines and their corresponding selective cytotoxicity (SI) was estimated using normal lung fibroblast (WI-38) cells. Most of the organic selenides exhibited good anticancer activity, and this was more pronounced in HepG2 cells. Interestingly, the naphthoquinone- (5), thiazol- (12), and the azo-based (13) organic selenides demonstrated promising SI (up to 76). Furthermore, the amine 4c, naphthoquinone 5, and azo-based 13 and 15 organic selenides were able to down-regulate the expression of Bcl-2 and up-regulate the expression levels of IL-2, IL-6 and CD40 in HepG2 cells compared to untreated cells. Moreover, most of the synthesized candidates manifested good free radical-scavenging and GPx-like activities comparable to vitamin C and ebselen. The obtained results suggested that some of the presented organoselenium candidates have promising anti-HepG2 and antioxidant activities.

Topics: Antineoplastic Agents; Antioxidants; Biphenyl Compounds; Breast Neoplasms; Carcinoma, Hepatocellular; Cell Line; Cell Proliferation; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Female; Hep G2 Cells; Humans; Liver Neoplasms; MCF-7 Cells; Molecular Structure; Organoselenium Compounds; Picrates; Structure-Activity Relationship

To investigate the effects of high dose vitamin C (VC) on proliferation of breast cancer cells and to explore its mechanisms.. Human breast cancer cells Bcap37 and MDA-MB-453 were treated with VC at low dose (0.01 mmol/L), medium dose (0.10 mmol/L) and high dose (2.00 mmol/L). Cell proliferation was determined with CCK-8 assay, protein expression was evaluated by Western blot, and the secretion of lactic acid in tumor cells was detected by colorimetric method. Bcap37 cells were inoculated in nude mice, and tumor baring nude mice were intraperitoneally injected with high VC(4 g/kg, VC group,. High dose VC may inhibit proliferation of breast cancer cells both

Topics: Animals; Ascorbic Acid; Breast Neoplasms; Cell Line, Tumor; Cell Proliferation; Glycolysis; Humans; Mice; Mice, Nude; Prohibitins; Protein Biosynthesis

Vitamin C (Vit C) is an important physiological antioxidant with growing applications in cancer. Somatostatin (SST) is a natural peptide with growth inhibitory effect in several mammary cancer models.. The combined effects of SST and Vit C supplementation have never been studied in breast cancer cells so far.. We used MCF-7 and MDA-MB231 breast cancer cells incubated with SST for 24h, in the absence and presence of Vit C, at their EC50 concentrations, to evaluate membrane fatty acid-profiles together with the follow-up of EGFR and MAPK signaling pathways.. The two cell lines gave different membrane reorganization: in MCF-7 cells, decrease of omega-6 linoleic acid and increase of omega-3 fatty acids (Fas) occurred after SST and SST+Vit C incubations, the latter also showing significant increases in MUFA, docosapentaenoic acid and mono-trans arachidonic acid levels. In MDA-MB231 cells, SST+Vit C incubation induced significant membrane remodeling with an increase of stearic acid and mono-trans-linoleic acid isomer, diminution of omega-6 linoleic, arachidonic acid and omega-3 (docosapentaenoic and docosadienoic acids). Distinct signaling pathways in these cell lines were studied: in MCF-7 cells, incubations with SST and Vit C, alone or in combination significantly decreased EGFR and MAPK signaling, whereas in MDA-MB231 cells, SST and Vit C incubations, alone or combined, decreased p- P44/42 MAPK levels, and increased EGFR levels.. Our results showed that SST and Vit C can be combined to induce membrane fatty acid changes, including lipid isomerization through a specific free radical-driven process, influencing signaling pathways.

Topics: Arachidonic Acids; Ascorbic Acid; Breast Neoplasms; Cell Extracts; Cell Line, Tumor; Cell Membrane; Fatty Acids; Fatty Acids, Omega-3; Fatty Acids, Unsaturated; Green Fluorescent Proteins; Humans; Lipids; Mitogen-Activated Protein Kinase Kinases; Phospholipids; Signal Transduction; Somatostatin; Stearic Acids

Topics: Ascorbic Acid; Breast Neoplasms; Female; Humans; Infusions, Intravenous; Pakistan

Epigenetic reprogramming by embryonic stem cell-specific miR-302/367 cluster has shown some tumor suppressive effects in cancer cells of different tissues such as skin, colon, and cervix. Vitamin C has been known as a reprogramming enhancer of human and mouse somatic cells. In this study, first we aimed to investigate whether exogenous induction of miR-302/367 in breast cancer cells shows the same tumor suppressive effects previously observed in other cancer cells lines, and whether vitamin C can enhance reprogramming of breast cancer cells and also improve the tumor suppressive function of miR-302/367 cluster. Overexpression of miR-302/367 cluster in MDA-MB-231 and SK-BR-3 breast cancer cells upregulated expression of miR-302/367 members and also some core pluripotency factors including OCT4A, SOX2 and NANOG, induced mesenchymal to epithelial transition, suppressed invasion, proliferation, and induced apoptosis in the both cell lines. However, treatment of the miR-302/367 transfected cells with vitamin C suppressed the expression of pluripotency factors and augmented the tumorigenicity of the breast cancer cells by restoring their proliferative and invasive capacity and compromising the apoptotic effect of miR-302/367. Supplementing the culture medium with vitamin C downregulated expression of TET1 gene which seems to be the reason behind the negative impact of vitamin C on the reprogramming efficiency of miR-302/367 cluster and its anti-tumor effects. Therefore application of vitamin C may not always serve as a reprogramming enhancer depending on its switching function on TET1. This phenomenon should be carefully considered when considering a reprogramming strategy for tumor suppression.

Topics: Ascorbic Acid; Breast Neoplasms; Cell Line, Tumor; Cell Movement; Cell Proliferation; Cellular Reprogramming; Down-Regulation; Epithelial-Mesenchymal Transition; Gene Expression Regulation, Neoplastic; Humans; MicroRNAs; Proto-Oncogene Proteins

Chronic stress triggers activation of the sympathetic nervous system and drives malignancy. Using an immunodeficient murine system, we showed that chronic stress-induced epinephrine promoted breast cancer stem-like properties via lactate dehydrogenase A-dependent (LDHA-dependent) metabolic rewiring. Chronic stress-induced epinephrine activated LDHA to generate lactate, and the adjusted pH directed USP28-mediated deubiquitination and stabilization of MYC. The SLUG promoter was then activated by MYC, which promoted development of breast cancer stem-like traits. Using a drug screen that targeted LDHA, we found that a chronic stress-induced cancer stem-like phenotype could be reversed by vitamin C. These findings demonstrated the critical importance of psychological factors in promoting stem-like properties in breast cancer cells. Thus, the LDHA-lowering agent vitamin C can be a potential approach for combating stress-associated breast cancer.

Topics: Animals; Ascorbic Acid; Breast Neoplasms; Epinephrine; Female; Humans; L-Lactate Dehydrogenase; MCF-7 Cells; Mice; Mice, Inbred NOD; Mice, SCID; Neoplastic Stem Cells; Proto-Oncogene Proteins c-myc; Snail Family Transcription Factors; Stress, Psychological

The anti-cancer effect of high doses of intravenous vitamin C (high-dose vitamin C) remains controversial despite growing evidence that high-dose vitamin C exerts anti-tumorigenic activity by increasing the amount of reactive oxygen species in cancer cells without meaningful toxicities. Therefore, this study attempted to demonstrate the in vitro anti-cancer activity of high-dose vitamin C in combination with conventional treatment in breast cancer.. The pro-apoptotic effects of high-dose vitamin C (1.25 to 20 mM) with or without anti-cancer agents (eribulin mesylate, tamoxifen, fulvestrant, or trastuzumab) were estimated using an MTT assay to measure the cell viability of a variety of breast cancer cell lines (MCF7, SK-BR3, and MDA-MB-231), as well as normal breast epithelial cells (MCF10A).. High-dose vitamin C (≥10 mM) significantly decreased cell viability of all breast cancer cell lines, particularly of MCF-7 cells. The catalase activities of MCF7 and MDA-MD-231 cells were also lower than those of MCF10A cells. Moreover, cell viability of both MCF7 and MDA-MD-231 cells was decreased further when combining high-dose vitamin C and eribulin mesylate, and this was also true for MCF-7 cells when combining high-dose vitamin C with tamoxifen or fulvestrant and for SK-BR3 cells when combining high-dose vitamin C with trastuzumab in comparison with chemotherapy or endocrine therapy alone.. Combining high-dose vitamin C with conventional anti-cancer drugs can have therapeutic advantages against breast cancer cells.

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Ascorbic Acid; Breast Neoplasms; Cell Line, Tumor; Cell Survival; Drug Screening Assays, Antitumor; Drug Synergism; Female; Fulvestrant; Furans; Humans; Ketones; MCF-7 Cells; Tamoxifen; Trastuzumab

The potential role of vitamin C in cancer prevention and treatment remains controversial. While normal human cells obtain vitamin C as ascorbic acid, the prevalent form of vitamin C in vivo, the uptake mechanisms by which cancer cells acquire vitamin C has remained unclear. The aim of this study is to characterize how breast cancer cells acquire vitamin C. For this, we determined the expression of vitamin C transporters in normal and breast cancer tissue samples, and in ZR-75, MCF-7, MDA-231 and MDA-468 breast cancer cell lines. At the same time, reduced (AA) and oxidized (DHA) forms of vitamin C uptake experiments were performed in all cell lines. We show here that human breast cancer tissues differentially express a form of SVCT2 transporter, that is systematically absent in normal breast tissues and it is increased in breast tumors. In fact, estrogen receptor negative breast cancer tissue, exhibit the most elevated SVCT2 expression levels. Despite this, our analysis in breast cancer cell lines showed that these cells are not able to uptake ascorbic acid and depend on glucose transporter for the acquisition of vitamin C by a bystander effect. This is consistent with our observations that this form of SVCT2 is completely absent from the plasma membrane and is overexpressed in mitochondria of breast cancer cells, where it mediates ascorbic acid transport. This work shows that breast cancer cells acquire vitamin C in its oxidized form and are capable of accumulated high concentrations of the reduced form. Augmented expression of an SVCT2 mitochondrial form appears to be a common hallmark across all human cancers and might have implications in cancer cells survival capacity against pro-oxidant environments.

Topics: Ascorbic Acid; Breast Neoplasms; Bystander Effect; Female; Gene Expression Regulation, Neoplastic; Humans; MCF-7 Cells; Mitochondria; Mitochondrial Membrane Transport Proteins; Oxidation-Reduction; Reactive Oxygen Species; Sodium; Sodium-Coupled Vitamin C Transporters

The transcription factor hypoxia inducible factor (HIF) -1 drives tumor growth and metastasis and is associated with poor prognosis in breast cancer. Ascorbate can moderate HIF-1 activity in vitro and is associated with HIF pathway activation in a number of cancer types, but whether tissue ascorbate levels influence the HIF pathway in breast cancer is unknown. In this study we investigated the association between tumor ascorbate levels and HIF-1 activation and patient survival in human breast cancer.. In a retrospective analysis of human breast cancer tissue, we analysed primary tumor and adjacent uninvolved tissue from 52 women with invasive ductal carcinoma. We measured HIF-1α, HIF-1 gene targets CAIX, BNIP-3 and VEGF, and ascorbate content. Patient clinical outcomes were evaluated against these parameters.. HIF-1 pathway proteins were upregulated in tumor tissue and increased HIF-1 activation was associated with higher tumor grade and stage, with increased vascular invasion and necrosis, and with decreased disease-free and disease-specific survival. Grade 1 tumors had higher ascorbate levels than did grade 2 or 3 tumors. Higher ascorbate levels were associated with less tumor necrosis, with lower HIF-1 pathway activity and with increased disease-free and disease-specific survival.. Our findings indicate that there is a direct correlation between intracellular ascorbate levels, activation of the HIF-1 pathway and patient survival in breast cancer. This is consistent with the known capacity of ascorbate to stimulate the activity of the regulatory HIF hydroxylases and suggests that optimisation of tumor ascorbate could have clinical benefit via modulation of the hypoxic response.

Topics: Antigens, Neoplasm; Ascorbic Acid; Breast Neoplasms; Carbonic Anhydrase IX; Carcinoma, Ductal, Breast; Cell Hypoxia; Cell Line, Tumor; Female; Gene Expression Regulation, Neoplastic; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Membrane Proteins; Middle Aged; Neoplasm Grading; Neoplasm Staging; Prognosis; Proto-Oncogene Proteins; Retrospective Studies; Survival Analysis; Up-Regulation; Vascular Endothelial Growth Factor A

Genomic loss of 5-hydroxymethylcytosine (5hmC) accompanies malignant cellular transformation in breast cancer. Vitamin C serves as a cofactor for TET methylcytosine dioxygenases to increase 5hmC generation. Here we show that the transcription of SVCT2, a major vitamin C transporter, was decreased in human breast cancers (113 cases) compared to normal breast tissues from the same patients. A decreased SVCT2 expression was also observed in breast cancer cell lines. Treatment with vitamin C (100 μM) increased the 5hmC content in MDA-MB-231 breast cancer cells and markedly altered the transcriptome. The vitamin C treatment induced apoptosis in MDA-MB-231 cells, which was verified in two additional breast cancer cell lines. This pro-apoptotic effect of vitamin C appeared to be mediated by TRAIL, a known apoptosis inducer. Vitamin C upregulated TRAIL transcripts (2.3-fold increase) and increased TRAIL protein levels. The upregulation of TRAIL by vitamin C was largely abolished by siRNAs targeting TETs and anti-TRAIL antibody abrogated the induction of apoptosis. Furthermore, the apoptosis promoted by vitamin C was associated with Bax and caspases activation, Bcl-xL sequestration, and cytochrome c release. Taken together, these results suggest a potential role of physiological doses of vitamin C in breast cancer prevention and treatment.

Topics: 5-Methylcytosine; Apoptosis; Ascorbic Acid; Breast Neoplasms; Cell Line, Tumor; Cell Survival; Female; Gene Expression Regulation, Neoplastic; Humans; MCF-7 Cells; Receptors, TNF-Related Apoptosis-Inducing Ligand; Sodium-Coupled Vitamin C Transporters; TNF-Related Apoptosis-Inducing Ligand

Our previous work has shown peroxiredoxin-1 (PRDX1), one of major antioxidant enzymes, to be a biomarker in human breast cancer. Hereby, we further investigate the role of PRDX1, compared to its close homolog PRDX2, in mammary malignant cells.. CRISPR/Cas9- or RNAi-based methods were used for genetic targeting PRDX1/2. Cell growth was assessed by crystal violet, EdU incorporation or colony formation assays. In vivo growth was assessed by a xenotransplantation model. Adenanthin was used to inhibit the thioredoxin-dependent antioxidant defense system. The prooxidant agents used were hydrogen peroxide, glucose oxidase and sodium L-ascorbate. A PY1 probe or HyPer-3 biosensor were used to detect hydrogen peroxide content in samples.. PRDX1 downregulation significantly impaired the growth rate of MCF-7 and ZR-75-1 breast cancer cells. Likewise, xenotransplanted PRDX1-deficient MCF-7 cells presented a retarded tumour growth. Furthermore, genetic targeting of PRDX1 or adenanthin, but not PRDX2, potently sensitised all six cancer cell lines studied, but not the non-cancerous cells, to glucose oxidase and ascorbate.. Our study pinpoints the dominant role for PRDX1 in management of exogeneous oxidative stress by breast cancer cells and substantiates further exploration of PRDX1 as a target in this disease, especially when combined with prooxidant agents.

Topics: Animals; Antioxidants; Ascorbic Acid; Breast Neoplasms; Cell Line, Tumor; Cell Proliferation; CRISPR-Cas Systems; Diterpenes, Kaurane; Female; Gene Knockdown Techniques; Glucose Oxidase; Humans; MCF-7 Cells; Mice; Oxidative Stress; Peroxiredoxins; RNA Interference; Up-Regulation; Xenograft Model Antitumor Assays

In the present investigation, synthesis of a series of extended conjugated δ-chloro-α-cyano substituted indolyl chalcones (5a-p) was accomplished by reacting 3-cyanoacetylindole 2 with 3-chloro-3-phenyl-propenal 4 in the presence of piperidine. The structural interpretations of newly synthesized compounds were based on chemical and spectroscopic evidences. Anti-tumor evaluation of the synthesized compounds in vitro against MCF-7 (breast carcinoma) cell line revealed that they possess high anti-tumor activities. Among them, compound 5e and 5a demonstrated excellent activity against breast carcinoma (GI

Topics: Albumins; Animals; Anti-Inflammatory Agents, Non-Steroidal; Antineoplastic Agents; Breast Neoplasms; Chalcones; Chlorocebus aethiops; Diclofenac; Doxorubicin; Egg Proteins; Female; Free Radical Scavengers; Humans; Indoles; MCF-7 Cells; Nitric Oxide; Protein Denaturation; Structure-Activity Relationship; Superoxides; Vero Cells

Doxorubicin is an anthracycline drug which inhibits the growth of breast cancer cell lines. However, a major factor limiting its use is a cumulative, dose-dependent cardiotoxicity, resulting in a permanent loss of cardiomyocytes. Vitamin C was found to potentiate the cytotoxic effects of a variety of chemotherapeutic drugs including doxorubicin. The aim of the study was to describe the changes in protein expression and proliferation of the MCF-7 cells induced by the vitamin C applied with doxorubicin.. Label-free quantitative proteomics and real-time cell analysis methods were used to search for proteome and cell proliferation changes. These changes were induced by the pure DOX and by DOX combined with vitamin C applied on the MCF-7 cell line.. From the real-time cell analysis experiments, it is clear that the highest anti-proliferative effect occurs with the addition of 200 µM of vitamin C to 1 µM of doxorubicin. By applying both the label-free protein quantification method and total ion current assay, we found statistically significant changes (p ≤ 0.05) of 26 proteins induced by the addition of vitamin C to doxorubicin on the MCF-7 cell line. These differentially expressed proteins are involved in processes such as structural molecule activity, transcription and translation, immune system process and antioxidant, cellular signalling and transport.. The detected proteins may be capable of predicting response to DOX therapy. This is a key tool in the treatment of breast cancer, and the combination with vit C seems to be of particular interest due to the fact that it can potentiate anti-proliferative effect of DOX.

Topics: Antibiotics, Antineoplastic; Antioxidants; Ascorbic Acid; Breast Neoplasms; Cell Proliferation; Doxorubicin; Drug Resistance, Neoplasm; Drug Screening Assays, Antitumor; Drug Synergism; Female; Humans; MCF-7 Cells; Proteome; Proteomics

Slow drug release at the tumor tissue and poor tumor penetration are two big challenges for the successful application of nanosystems in tumor therapy. Here, we report that a high concentration of the natural reducing agent vitamin C (VC) triggers rapid extracellular PTX release from PTX-loaded shell-sheddable PEG-SS-PCL micelles (SSM) in tumors in vivo. An in vivo tolerance study showed that VC at a blood concentration of 40mM had little toxicity to nude mice. Notably, SSM rapidly disassembled and released the payloads (Cy5 or PTX) in response to 40mM VC. In vivo near-infrared imaging of tumor-bearing mice showed that with post-injection of VC to establish a blood concentration of 40mM, Cy5 was quickly released from the micelles and diffused deep into the tumor tissue. Biodistribution studies revealed that 6h after the injection of PTX-loaded micelles the highest tumor accumulation was reached, which was set as the injection time for VC. The antitumor efficacy of a combination therapy of PTX-loaded micelles and VC was evaluated in both MCF-7 and U87MG tumor models. In both tumor models, single injections of VC didn't show any antitumor effect, while sequential administration of PTX-loaded SSM and VC exhibited significantly higher tumor inhibition effects and better survival rates as compared to single treatment with PTX-loaded micelles, demonstrating that exogenous administration of VC effectively triggered the release of PTX from SSM in vivo. The combination of reduction-sensitive nanomedicines with exogenous VC appears a promising approach to achieve potent treatment of malignant tumors.

Topics: Animals; Antineoplastic Agents; Ascorbic Acid; Breast Neoplasms; Carbocyanines; Cell Line, Tumor; Delayed-Action Preparations; Drug Carriers; Drug Liberation; Drug Synergism; Female; Humans; Mice; Mice, Inbred BALB C; Mice, Nude; Micelles; Neoplasm Transplantation; Oxidation-Reduction; Paclitaxel; Polyesters; Polyethylene Glycols; Succinimides; Surface Properties

Topics: Aged, 80 and over; Ascorbate Oxidase; Ascorbic Acid; Breast Neoplasms; Cholesterol; Colorimetry; Enzyme Assays; Female; Humans; Injections, Intravenous; Intestine, Small; Kidney; Male; Middle Aged; Palliative Care; Recurrence

Carotenoids and vitamin C are thought to be associated with reduced cancer risk because of their antioxidative capacity.. This study evaluated the associations of plasma carotenoid, retinol, tocopherol, and vitamin C concentrations and risk of breast cancer.. In a nested case-control study within the European Prospective Investigation into Cancer and Nutrition cohort, 1502 female incident breast cancer cases were included, with an oversampling of premenopausal (n = 582) and estrogen receptor-negative (ER-) cases (n = 462). Controls (n = 1502) were individually matched to cases by using incidence density sampling. Prediagnostic samples were analyzed for α-carotene, β-carotene, lycopene, lutein, zeaxanthin, β-cryptoxanthin, retinol, α-tocopherol, γ-tocopherol, and vitamin C. Breast cancer risk was computed according to hormone receptor status and age at diagnosis (proxy for menopausal status) by using conditional logistic regression and was further stratified by smoking status, alcohol consumption, and body mass index (BMI). All statistical tests were 2-sided.. In quintile 5 compared with quintile 1, α-carotene (OR: 0.61; 95% CI: 0.39, 0.98) and β-carotene (OR: 0.41; 95% CI: 0.26, 0.65) were inversely associated with risk of ER- breast tumors. The other analytes were not statistically associated with ER- breast cancer. For estrogen receptor-positive (ER+) tumors, no statistically significant associations were found. The test for heterogeneity between ER- and ER+ tumors was statistically significant only for β-carotene (P-heterogeneity = 0.03). A higher risk of breast cancer was found for retinol in relation to ER-/progesterone receptor-negative tumors (OR: 2.37; 95% CI: 1.20, 4.67; P-heterogeneity with ER+/progesterone receptor positive = 0.06). We observed no statistically significant interaction between smoking, alcohol, or BMI and all investigated plasma analytes (based on tertile distribution).. Our results indicate that higher concentrations of plasma β-carotene and α-carotene are associated with lower breast cancer risk of ER- tumors.

Topics: Adult; Antioxidants; Ascorbic Acid; beta Carotene; Breast Neoplasms; Carotenoids; Case-Control Studies; Cohort Studies; Diet; Europe; Female; Follow-Up Studies; Humans; Middle Aged; Neoplasm Proteins; Postmenopause; Premenopause; Prospective Studies; Receptors, Estrogen; Risk; Tocopherols; Vitamin A

Abnormal expression of NRF2 levels in some tumor tissues may enhance drug resistance through various mechanisms. Recent studies have demonstrated a link between dysregulated expression of miRNAs and breast carcinogenesis.. Quantitative RT-PCR analysis was used to examine the expression levels of miR-153 in breast cancer cell lines. The biological effects of miR-153 were assessed in CRC cell lines using clonogenic cell survival assay, mammosphere formation assay, cell migration assay, 8-OHdG estimation assay, and flow cytometry analysis. Quantitative RT-PCR and western blot analyses were employed to evaluate the expression of miR-153 targets. In this study, we investigated the role of vitamin C in the regulation of miR-153 (miR-153) and its target gene(s) in cell models of mammary carcinogenesis.. In human breast cell lines treated with E2, the level of miR-153 was found to be increased. In contrast, vitamin C treatment was able to decrease the expression of miR-153. Bioinformatic prediction indicates nuclear factor erythroid 2-related factor 2 (NRF2) may be a target for miR-153. In E2-treated breast cancer cell lines, NRF2 protein level was found to be decreased. Overexpression of miR-153 significantly reduced NRF2 and the downstream genes. Furthermore, miR-153 was found to decrease apoptosis and increase colony formation in breast epithelial cells.. These data indicate that miR-153 acts as an oncogene in breast carcinogenesis by targeting NRF2.

Topics: Animals; Apoptosis; Ascorbic Acid; Breast Neoplasms; Cell Line, Tumor; Cell Movement; Cell Proliferation; Computational Biology; Estradiol; Female; Gene Expression Regulation, Neoplastic; Humans; Mammary Glands, Animal; MicroRNAs; NF-E2-Related Factor 2; Oxidative Stress; Rats, Sprague-Dawley; RNA Interference; Signal Transduction; Transfection

Experimental and epidemiologic studies have yielded conflicting results on the relation between vitamin C intake and breast cancer risk.. We investigated the relation between vitamin C supplement intake and breast cancer risk while considering dietary vitamin C intake.. Between 1995 and 2008, 2482 invasive breast cancer cases occurred in 57,403 postmenopausal women from the Etude Epidémiologique auprès de femmes de la Mutuelle Générale de l'Education Nationale (E3N) prospective cohort during 581,085 person-years. We estimated vitamin C intake from foods with the use of a validated food-frequency questionnaire that was sent to subjects in 1993-1995 and vitamin C supplement use via questionnaires sent in 1995, 2000, 2002, and 2005. Multivariable HRs (95% CIs) for primary invasive breast cancer were estimated with the use of Cox regression models. All statistical tests were 2-sided.. Vitamin C supplement use (ever compared with never) was not associated with breast cancer risk overall; it was associated with higher breast cancer risk in women in the fourth quartile of vitamin C intake from foods (HR: 1.32; 95% CI: 1.04, 1.67) but not in other quartiles of dietary vitamin C intake (P-interaction = 0.03).. We observed that vitamin C supplement use was associated with increased postmenopausal breast cancer risk in women with high vitamin C intake from foods. Our data suggest a potential U- or J-shaped relation between total vitamin C intake and postmenopausal breast cancer risk that deserves further investigation.

Topics: Aged; Ascorbic Acid; Breast Neoplasms; Diet; Dietary Supplements; Female; Humans; Middle Aged; Postmenopause; Proportional Hazards Models; Prospective Studies; Risk Factors; Surveys and Questionnaires; Vitamins

Pharmacological concentrations of small molecule natural products, such as ascorbic acid, have exhibited distinct cell killing outcomes between cancer and normal cells whereby cancer cells undergo apoptosis or necrosis while normal cells are not adversely affected. Here, we develop a mathematical model for ascorbic acid that can be utilized as a tool to understand the dynamics of reactive oxygen species (ROS) induced cell death. We determine that not only do endogenous antioxidants such as catalase contribute to ROS-induced cell death, but also cell membrane properties play a critical role in the efficacy of ROS as a cytotoxic mechanism against cancer cells vs. normal cells. Using in vitro assays with breast cancer cells, we have confirmed that cell membrane properties are essential for ROS, in the form of hydrogen peroxide (H2O2), to induce cell death. Interestingly, we did not observe any correlation between intracellular H2O2 and cell survival, suggesting that cell death by H2O2 is triggered by interaction with the cell membrane and not necessarily due to intracellular levels of H2O2. These findings provide a putative mechanistic explanation for the efficacy and selectivity of therapies such as ascorbic acid that rely on ROS-induced cell death for their anti-tumor properties.

Topics: Antineoplastic Agents; Antioxidants; Apoptosis; Ascorbic Acid; Breast Neoplasms; Catalase; Cell Death; Cell Line, Tumor; Cell Membrane; Cell Survival; Female; Humans; Hydrogen Peroxide; Models, Theoretical; Necrosis; Reactive Oxygen Species

Vitamin C is an essential dietary nutrient that has a variety of biological functions. Recent studies have provided promising evidence for its additional health benefits, including anticancer activity. Vitamin B2, another essential dietary nutrient, often coexists with vitamin C in some fruits, vegetables, or dietary supplements. The objective of the present study is to determine whether the combination of vitamin C and B2 can achieve a synergistic anticancer activity. MDA-MB-231, MCF-7, and A549 cells were employed to evaluate the combinatory effects of vitamin C and B2. We found that the combination of vitamin C and B2 resulted in a synergistic cell death induction in all cell lines tested. Further mechanistic investigations revealed that vitamin B2 sensitized cancer cells to vitamin C through inhibition of Akt and Bad phosphorylation. Our findings identified vitamin B2 as a promising sensitizer for improving the efficacy of vitamin-C-based cancer chemoprevention and chemotherapy.

Topics: Apoptosis; Ascorbic Acid; bcl-Associated Death Protein; Breast Neoplasms; Cell Line, Tumor; Drug Synergism; Female; Humans; Phosphorylation; Proto-Oncogene Proteins c-akt; Riboflavin

Adjuvant Nutritional Intervention in Cancer (ANICA) was a clinical study carried out in Denmark in the 1990s with 32 typical patients with breast cancer, aged 32-81 yr and classified high risk because of tumor spread to the lymph nodes. The patients received standard therapy for their breast cancer, but got from the start additionally an adjuvant therapy in form of a cocktail consisting of vitamin C (2,850 mg/day), vitamin E (2,500 IU/day), beta-carotene (32.5 IU/day), selenium (Se; 387 micrograms/day), various other vitamins and essential trace elements, essential fatty acids (1.2 g gamma-linolenic acid/day and 3.5 g omega-3 PUFAs/day), and coenzyme Q10 (CoQ10, 90 mg/day). The protocol was later changed, with reduction of the Se intake and more coenzyme Q10 than when the study was started. The average survival of high-risk breast patients in the study was 50% after 5 yr, whereas for low-risk breast cancer patients (without metastases in the axilla when treatment was started), the average survival was 90% after ten years. The main investigator died, and the final report from the ANICA study was therefore never written. However, the published preliminary results from the trial were very promising; it seems, therefore, important to follow-up this study.

Topics: Adult; Aged; Aged, 80 and over; Ascorbic Acid; beta Carotene; Breast Neoplasms; Chemotherapy, Adjuvant; Clinical Trials as Topic; Denmark; Fatty Acids, Essential; Female; Humans; Lymphatic Metastasis; Middle Aged; Nutrition Therapy; Selenium; Survival Rate; Trace Elements; Ubiquinone; Vitamin E; Vitamins

Ascorbate (Asc) as a single agent suppressed growth of several tumor cell lines in a mouse model. It has been tested in a Phase I Clinical Trial on pancreatic cancer patients where it exhibited no toxicity to normal tissue yet was of only marginal efficacy. The mechanism of its anticancer effect was attributed to the production of tumoricidal hydrogen peroxide (H2O2) during ascorbate oxidation catalyzed by endogenous metalloproteins. The amount of H2O2 could be maximized with exogenous catalyst that has optimized properties for such function and is localized within tumor. Herein we studied 14 Mn porphyrins (MnPs) which differ vastly with regards to their redox properties, charge, size/bulkiness and lipophilicity. Such properties affect the in vitro and in vivo ability of MnPs (i) to catalyze ascorbate oxidation resulting in the production of H2O2; (ii) to subsequently employ H2O2 in the catalysis of signaling proteins oxidations affecting cellular survival pathways; and (iii) to accumulate at site(s) of interest. The metal-centered reduction potential of MnPs studied, E1/2 of Mn(III)P/Mn(II)P redox couple, ranged from -200 to +350 mV vs NHE. Anionic and cationic, hydrophilic and lipophilic as well as short- and long-chained and bulky compounds were explored. Their ability to catalyze ascorbate oxidation, and in turn cytotoxic H2O2 production, was explored via spectrophotometric and electrochemical means. Bell-shape structure-activity relationship (SAR) was found between the initial rate for the catalysis of ascorbate oxidation, vo(Asc)ox and E1/2, identifying cationic Mn(III) N-substituted pyridylporphyrins with E1/2>0 mV vs NHE as efficient catalysts for ascorbate oxidation. The anticancer potential of MnPs/Asc system was subsequently tested in cellular (human MCF-7, MDA-MB-231 and mouse 4T1) and animal models of breast cancer. At the concentrations where ascorbate (1mM) and MnPs (1 or 5 µM) alone did not trigger any alteration in cell viability, combined treatment suppressed cell viability up to 95%. No toxicity was observed with normal human breast epithelial HBL-100 cells. Bell-shape relationship, essentially identical to vo(Asc)oxvs E1/2, was also demonstrated between MnP/Asc-controlled cytotoxicity and E1/2-controlled vo(Asc)ox. Magnetic resonance imaging studies were conducted to explore the impact of ascorbate on T1-relaxivity. The impact of MnP/Asc on intracellular thiols and on GSH/GSSG and Cys/CySS ratios in 4T1 cells was assessed and cellular

Topics: Animals; Antineoplastic Agents; Antioxidants; Apoptosis; Ascorbic Acid; Blotting, Western; Breast; Breast Neoplasms; Catalysis; Cell Proliferation; Cells, Cultured; Drug Therapy, Combination; Female; Humans; Hydrogen Peroxide; Immunoenzyme Techniques; Metalloporphyrins; Mice; Mice, Inbred BALB C; Oxidants; Oxidation-Reduction; Oxidative Stress; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Superoxide Dismutase; Xenograft Model Antitumor Assays

Resistance to therapy-mediated apoptosis in inflammatory breast cancer, an aggressive and distinct subtype of breast cancer, was recently attributed to increased superoxide dismutase (SOD) expression, glutathione (GSH) content, and decreased accumulation of reactive species. In this study, we demonstrate the unique ability of two Mn(III) N-substituted pyridylporphyrin (MnP)-based SOD mimics (MnTE-2-PyP(5+) and MnTnBuOE-2-PyP(5+)) to catalyze oxidation of ascorbate, leading to the production of excessive levels of peroxide, and in turn cell death. The accumulation of peroxide, as a consequence of MnP+ascorbate treatment, was fully reversed by the administration of exogenous catalase, showing that hydrogen peroxide is essential for cell death. Cell death as a consequence of the action of MnP+ascorbate corresponded to decreases in GSH levels, prosurvival signaling (p-NF-κB, p-ERK1/2), and in expression of X-linked inhibitor of apoptosis protein, the most potent caspase inhibitor. Although markers of classical apoptosis were observed, including PARP cleavage and annexin V staining, administration of a pan-caspase inhibitor, Q-VD-OPh, did not reverse the observed cytotoxicity. MnP+ascorbate-treated cells showed nuclear translocation of apoptosis-inducing factor, suggesting the possibility of a mechanism of caspase-independent cell death. Pharmacological ascorbate has already shown promise in recently completed phase I clinical trials, in which its oxidation and subsequent peroxide formation was catalyzed by endogenous metalloproteins. The catalysis of ascorbate oxidation by an optimized metal-based catalyst (such as MnP) carries a large therapeutic potential as an anticancer agent by itself or in combination with other modalities such as radio- and chemotherapy.

Topics: Apoptosis; Ascorbic Acid; Breast Neoplasms; Caspases; Female; Humans; Hydrogen Peroxide; Metalloporphyrins; NF-kappa B; Oxidation-Reduction; Peroxides; Reactive Oxygen Species; Superoxide Dismutase

Fatigue is a common, often debilitating, side effect of cancer chemotherapy. Pharmacologic vitamin C has been used as an alternative treatment for the disease itself but its effects on fatigue have not often been documented. Here we report on the case of a woman with recurrent breast cancer, undergoing weekly chemotherapy, with lethargy as a major symptom. Vitamin C (50 g/session) was administered twice weekly and quality of life and multidimensional fatigue symptomology questionnaires were undertaken. Dramatic decreases in fatigue and insomnia were observed, as well as increased cognitive functioning. There were no adverse side effects of i.v. vitamin C.

Topics: Antineoplastic Combined Chemotherapy Protocols; Ascorbic Acid; Breast Neoplasms; Carcinoma, Intraductal, Noninfiltrating; Dose-Response Relationship, Drug; Drug Administration Schedule; Fatigue; Female; Follow-Up Studies; Humans; Middle Aged; Neoplasm Recurrence, Local; Quality of Life; Severity of Illness Index; Treatment Outcome

In the present study, the radiation-induced effect of cytochrome c (CytC) and vitamin C (VitC) is studied with respect to survival of MCF-7 cancer cells grown in aerated media. Both, CytC and VitC, were incubated with MCF-7 cancer cells under various concentrations individually, as well as in mixture and cells were subsequently treated with γ-ray in a dose range of 0 to 30 Gy. Generally, an increase of cell survival was observed under substance treatment up to a radiation dose of 5 Gy compared to the control group. Based on the obtained results it is believed that cell survival depends strongly on the action of free radicals produced at the given concentration of the incubated CytC and VitC as well as on the specific reaction rate constants (k: l mol(-1) s(-1)) of the involved processes.

Topics: Antioxidants; Apoptosis; Ascorbic Acid; Breast Neoplasms; Cell Proliferation; Cytochromes c; Female; Free Radicals; Gamma Rays; Humans; Radiation-Sensitizing Agents; Tumor Cells, Cultured

The main goal of this study is to investigate the expression of sodium dependent vitamin C transport system (SVCT2). Moreover, this investigation has been carried out to define uptake mechanism and intracellular regulation of ascorbic acid (AA) in human breast cancer cells (MDA-MB231, T47D and ZR-75-1). Uptake of [(14)C] AA was studied in MDA-MB231, T47D and ZR-75-1 cells. Functional parameters of [(14)C] AA uptake were delineated in the presence of different concentrations of unlabeled AA, pH, temperature, metabolic inhibitors, substrates and structural analogs. Molecular identification of SVCT2 was carried out with reverse transcription-polymerase chain reaction (RT-PCR). Uptake of [(14)C] AA was studied and found to be sodium, chloride, temperature, pH and energy dependent in all breast cancer cell lines. [(14)C] AA uptake was found to be saturable, with Km values of 53.85 ± 6.24, 49.69 ± 2.83 and 45.44 ± 3.16 μM and Vmax values of 18.45 ± 0.50, 32.50 ± 0.43 and 33.25 ± 0.53 pmol/min/mg protein, across MDA-MB231, T47D and ZR-75-1, respectively. The process is inhibited by structural analogs (l-AA and d-iso AA) but not by structurally unrelated substrates (glucose and PAHA). Ca(++)/calmodulin and protein kinase pathways appeared to play a crucial role in modulating AA uptake. A 626 bp band corresponding to a vitamin C transporter (SVCT2) based on the primer design was detected by RT-PCR analysis in all breast cancer cell lines. This research article describes AA uptake mechanism, kinetics, and regulation by sodium dependent vitamin C transporter (SVCT2) in MDA-MB231, T47D and ZR-75-1 cells. Also, MDA-MB231, T47D and ZR-75-1 cell lines can be utilized as a valuable in vitro model to investigate absorption and permeability of AA-conjugated chemotherapeutics.

Topics: Ascorbic Acid; Breast Neoplasms; Female; Humans; Hydrogen-Ion Concentration; Sodium-Coupled Vitamin C Transporters; Temperature; Time Factors; Tumor Cells, Cultured

A novel strategy for efficient "nanodelivery" of DNA-cleaving molecules for breast cancer regression is presented here. The synthetic methodology can be tweaked for controlled delivery and better bioavailability of effective doses of these DNA-cleaving agents through a defined self-assembled polymeric nanoarchitecture. In vitro studies in ER+ and ER- breast cancer human cell lines confirmed an efficient "nano"-delivery of DNA-cleaving molecules and indicated their capability to mediate oxidative damage to nucleobases and/or to the 2-deoxyribose moiety. Prepared E-poly-DNA-cleaver and C-poly-DNA-cleaver were found to be interacting with plasmid DNA pBR322 (pDNA) and active to cause oxidative cleavage of pDNA in the presence of ascorbic acid and H2O2. They were found to be significantly active as DNA cleaving agents in vitro and showed highly improved cancer regression in MCF-7 and MD-MB231 cancer cells compared to small molecule DNA cleaver. Surface conjugated nanoparticles were found to be more effective than noncovalent encapsulation and the small molecule agent, whereas in all the cases RCM was significantly inactive toward DNA cleavage. Blood contact complement activation properties were evaluated to gauge their likelihood to promote acute toxicity following systemic administration. The complement activation analyses together with the blood smear study confirm the feasibility of using these poly-DNA-cleavers without risk of induced immune response.

Topics: Antioxidants; Ascorbic Acid; Breast Neoplasms; DNA, Neoplasm; Drug Delivery Systems; Female; Humans; Hydrogen Peroxide; Nanoparticles; Oxidants; Oxidative Stress; Polymers; Receptors, Estrogen; Receptors, Progesterone; Regression Analysis; Small Molecule Libraries

Research indicates that oxidative stress induced by smoking plays a role in breast cancer. In view of these reports, we aimed to study th relationship between smoking and oxidative stress in breast cancer patients from the western region of Nepal.. The study included a control group of 42 females (non-smoking healthy women) and a test group sudivided into Group I consisting of 46 female breast cancer patients who were smokers and Group II consisting of 42 non-smoking breast cancer patients. Detailed history of the patients was collected with the help of pre-test proforma. Plasma levels of malondialdehyde (MDA), total antioxidant activity (TAA) which represents total dietary antioxidants, vitamin C and α- tocopherol were estimated by standard methods. Statistical analysis was done using SPSS version 16.. The plasma MDA, TAA, vitamin C and α- tocopherol were 1±1.4nmol/ml, 918±207μmol/L, 1±0.24mg/dL and 0.94±0.31mg/dL in controls, 5±1.2nmol/ml, 458±166 μmol/L, 0.64±0.32mg/dL and 0.5±0.3mg/dL in Group-I and 2.56±1.2nmol/ml, 663±178 μmol/L, 0.78±0.2mg/dL and 0.77±0.2mg/dL in Group- II, respectively. Vitamin C, α- tocopherol and TAA (p=0.001) were significantly reduced whereas MDA (p=0.001) was significantly raised in Group-I when compared to controls and Group-II.. We observed a significant rise in oxidative stress and low levels of antioxidants in breast cancer patients with smoking habit. It is well known that free radicals facilitate the progression of breast cancer, possibly increasing the risk of progression to the next stage.

Topics: Adult; alpha-Tocopherol; Antioxidants; Ascorbic Acid; Breast Neoplasms; Female; Humans; Malondialdehyde; Middle Aged; Nepal; Oxidative Stress; Smoking

Cancer cells are known to exhibit different hallmarks compared with normal cells. Therefore, targeting these features may improve the response to cancer therapy. In this study, we provided direct evidence that the α-tocopherol derivative ESeroS-GS inhibited the viability, migration, and invasion of breast cancer cells. ESeroS-GS induced cell death in different cancer cells in a dose-dependent manner but showed no significant effects on MCF-10A mammary epithelial cells. Although the ESeroS-GS-induced cell death in MDA-MB-231 breast cancer cells was accompanied with the generation of reactive oxygen species and the down regulation of mitochondrial membrane potential (MMP), no such effect on reactive oxygen species and MMP was seen in MCF-10A cells. Further studies indicated that ESeroS-GS down-regulated the expression of hexokinase II, SDH B, UQCRC2 and COX II in MDA-MB-231 cells but not in MCF-10A cells. The down-regulation of these enzymes accounts for the decreased oxidative phosphorylation (OXPHOS) and glycolysis in MDA-MB-231 cells upon ESeroS-GS treatment. We also found that sub-toxic concentration of ESeroS-GS treatment resulted in the impairment of F-actin cytoskeleton assembly and the consequently decreased migratory and invasive ability of MDA-MB-231 cells, which might be due to the inhibition of cellular energy metabolism. These results indicate that ESeroS-GS shows potential to become a novel anti-cancer agent by targeting the energy metabolism of cancer cells.

Topics: Adenosine Triphosphate; alpha-Tocopherol; Animals; Antineoplastic Agents; Antioxidants; Ascorbic Acid; Benzopyrans; Breast Neoplasms; Cell Line; Cell Line, Tumor; Cell Movement; Cell Survival; Chromans; Dose-Response Relationship, Drug; Energy Metabolism; Female; Glycolysis; HeLa Cells; Humans; Indoles; Mammary Glands, Human; Membrane Potential, Mitochondrial; Mice; Neoplasm Invasiveness; NIH 3T3 Cells; Oxidative Phosphorylation; Reactive Oxygen Species; Vitamin E

In recent years the use of natural dietary antioxidants to minimize the cytotoxicity and the damage induced in normal tissues by antitumor agents is gaining consideration. In literature, it is reported that vitamin C exhibits some degree of antineoplastic activity whereas Mitoxantrone (MTZ) is a synthetic anti-cancer drug with significant clinical effectiveness in the treatment of human malignancies but with severe side effects. Therefore, we have investigated the effect of vitamin C alone or combined with MTZ on MDA-MB231 and MCF7 human breast cancer cell lines to analyze their dose-effect on the tumor cellular growth, cellular death, cell cycle and cell signaling. Our results have evidenced that there is a dose-dependence on the inhibition of the breast carcinoma cell lines, MCF7 and MDA-MB231, treated with vitamin C and MTZ. Moreover, their combination induces: i) a cytotoxic effect by apoptotic death, ii) a mild G2/M elongation and iii) H2AX and mild PI3K activation. Hence, the formulation of vitamin C with MTZ induces a higher cytotoxicity level on tumor cells compared to a disjointed treatment. We have also found that the vitamin C enhances the MTZ effect allowing the utilization of lower chemotherapic concentrations in comparison to the single treatments.

Topics: Antineoplastic Agents; Antioxidants; Apoptosis; Ascorbic Acid; Breast Neoplasms; Cell Line, Tumor; Female; G2 Phase Cell Cycle Checkpoints; Histones; Humans; M Phase Cell Cycle Checkpoints; MCF-7 Cells; Mitoxantrone; Phosphatidylinositol 3-Kinases; Signal Transduction

The chloroform-methanol extract of Euryops arabicus, collected from Saudi provenance, yielded a new kaurane diterpene (1) and seven methoxylated flavones (2-8), two of which are new (2 and 3). Structures of the compounds were elucidated through interpretation of spectral data of NMR, MS and comparison with literature values. All compounds were evaluated for their anti-tumor activities, employing four different cancer cell lines (WI-38, VERO, HepG2 and MCF-7), ABTS free radical scavenging and immunemodulatory effects. All metabolites had considerable antioxidant and immunestimulatory effects. All compounds showed anticancer activity with IC₅₀ in range 10-125 μM, whilst 2 and 6 showed significant anti-proliferative activity against HepG2 (IC₅₀ = 20 and 15 μM) and MCF-7 (IC₅₀ = 15 and 10 μM), respectively. This effect was attributed to significant S-phase cell cycle arrest.

Topics: Antineoplastic Agents; Asteraceae; Breast Neoplasms; Flavonoids; Hep G2 Cells; Humans; Inhibitory Concentration 50; MCF-7 Cells; Safety; Saudi Arabia

MicroRNAs (miRNA) are small non-coding RNAs that regulate the expression of approximately 60% of all human genes and play important roles in disease processes. Recent studies have demonstrated a link between dysregulated expression of miRNAs and breast carcinogenesis. Long-term estrogen exposure is implicated in development of human breast cancers, yet underlying mechanisms remain elusive. We have recently demonstrated that antioxidant vitamin C (vit C) prevents estrogen-induced breast tumor development. In this study, we investigated the role of vit C in the regulation of microRNA-93 (miR-93) and its target gene(s) in a rat model of mammary carcinogenesis. Female August Copenhagen Irish (ACI) rats were treated with vit C in the presence or absence of 17β-estradiol (E2) for 8 months. We demonstrate an increased expression of the miR-93 in E2-treated mammary tissues and in human breast cell lines and vit C treatment reverted E2-mediated increase in miR-93 levels. MiRNA target prediction programs suggest one of the target genes of miR-93 to be nuclear factor erythroid 2-related factor 2 (NRF2). In contrast with miR-93 expression, NRF2 protein expression was significantly decreased in E2-treated mammary tissues, mammary tumors, and in breast cancer cell lines, and its expression was significantly increased after vit C treatment. Ectopic expression of miR-93 decreased protein expression of NRF2 and NRF2-regulated genes. Furthermore, miR-93 decreased apoptosis, increased colony formation, mammosphere formation, cell migration and DNA damage in breast epithelial cells, whereas silencing of miR-93 in these cells inhibited these carcinogenic processes. Taken together, our findings suggest an oncogenic potential of miR-93 during E2-induced breast carcinogenesis.

Topics: Animals; Apoptosis; Ascorbic Acid; Breast Neoplasms; Cell Line, Tumor; Cell Movement; Cell Transformation, Neoplastic; DNA Damage; Estradiol; Estrogens; Female; Humans; MicroRNAs; NF-E2-Related Factor 2; Rats; Rats, Inbred ACI; Rats, Sprague-Dawley; Up-Regulation

A series of new diethyl(alkyl/aryl/heteroarylamino)(4-(pyridine-2-yl)phenyl)methylphosphonates (4a-t) were synthesized via three-component Kabachnik-Field's reaction of 4-(pyridin-2-yl)benzaldehyde, diethylphosphite and various primary amines, catalyzed by cupric acetate monohydrate [Cu(OAc)(2) ∙ H(2)O] under solvent-free and microwave irradiation conditions. Their computational docking analysis supported them as good therapeutic agents to the breast cancer aromatase enzyme and ascertained 4a, 4h, 4m, 4n, and 4t as potential molecules with good binding affinities varying from -9.0 to -9.6 kcal/mol and containing the 4-(pyridine-2-yl)phenyl moiety as a pharmacophore. Their in vitro screening performed for the anti-cell proliferation activity against MBC-MCF7 cells by MTT and Trypan blue assays confirmed 4m, 4n, and 4q as promising compounds to sustain a low percentage of cell viability at 20 µg/mL concentration. These compounds were also evaluated for their antioxidant activity by the DPPH method and the results established that compounds 4m, 4n, and 4q show around 10% higher activity than the standard antioxidant ascorbic acid.

Topics: Antineoplastic Agents; Antioxidants; Ascorbic Acid; Breast Neoplasms; Cell Proliferation; Cell Survival; Female; Humans; MCF-7 Cells; Molecular Docking Simulation; Organophosphonates; Structure-Activity Relationship

Vitamin C may influence cancer progression through its antioxidant properties. However, the evidence from observational epidemiologic studies on vitamin C intake and survival following breast cancer diagnosis is not consistent, and the safety of vitamin C supplements following breast cancer diagnosis has not been extensively studied.. Using a food-frequency questionnaire we investigated whether vitamin C intake was associated with survival among 3405 women diagnosed with invasive breast cancer in the Swedish Mammography Cohort.. From 1987-2010, there were 1055 total deaths with 416 deaths from breast cancer. Women in the highest quartile of pre-diagnosis vitamin C intake had an adjusted HR (95% CI) of breast cancer death of 0.75 (0.57-0.99) compared with those in the lowest quartile (Ptrend=0.03). There was a borderline significant association between vitamin C intake and total mortality (HR=0.84; 95% CI=0.71-1.00; Ptrend=0.08). Among 717 breast cancer cases for whom post-diagnosis supplement use was available, there was no association between vitamin C supplement use (≈1000 mg) and breast cancer-specific mortality (HR=1.06; 95% CI=0.52-2.17).. Our findings suggest that dietary vitamin C intake before breast cancer diagnosis may be associated with breast cancer survival. In addition, post-diagnosis vitamin C supplementation at the level observed in our population was not associated with survival.

Topics: Antioxidants; Ascorbic Acid; Breast Neoplasms; Diet; Dietary Supplements; Female; Food Preferences; Humans; Middle Aged; Surveys and Questionnaires; Survival Analysis; Sweden

Metastasis by cancer cells relies upon the acquisition of the ability to evade anoikis, a cell death process elicited by detachment from extracellular matrix (ECM). The molecular mechanisms that ECM-detached cancer cells use to survive are not understood. Striking increases in reactive oxygen species (ROS) occur in ECM-detached mammary epithelial cells, threatening cell viability by inhibiting ATP production, suggesting that ROS must be neutralized if cells are to survive ECM-detachment. Here, we report the discovery of a prominent role for antioxidant enzymes, including catalase and superoxide dismutase, in facilitating the survival of breast cancer cells after ECM-detachment. Enhanced expression of antioxidant enzymes in nonmalignant mammary epithelial cells detached from ECM resulted in ATP elevation and survival in the luminal space of mammary acini. Conversely, silencing antioxidant enzyme expression in multiple breast cancer cell lines caused ATP reduction and compromised anchorage-independent growth. Notably, antioxidant enzyme-deficient cancer cells were compromised in their ability to form tumors in mice. In aggregate, our results reveal a vital role for antioxidant enzyme activity in maintaining metabolic activity and anchorage-independent growth in breast cancer cells. Furthermore, these findings imply that eliminating antioxidant enzyme activity may be an effective strategy to enhance susceptibility to cell death in cancer cells that may otherwise survive ECM-detachment.

Topics: Adenosine Triphosphate; Animals; Antioxidants; Ascorbic Acid; Blotting, Western; Breast Neoplasms; Catalase; Catechin; Cell Adhesion; Cell Line; Cell Line, Tumor; Cell Survival; Chromans; Extracellular Matrix; Female; Humans; Mice; Mice, Nude; Reactive Oxygen Species; RNA Interference; Superoxide Dismutase; Tomography, X-Ray Computed; Xenograft Model Antitumor Assays

L-ascorbate (L-ascorbic acid, vitamin C) clearly has an inhibitory effect on cancer cells. However, the mechanism underlying differential sensitivity of cancer cells from same tissue to L-ascorbate is yet to be clarified. Here, we demonstrate that L-ascorbate has a selective killing effect, which is influenced by sodium-dependent vitamin C transporter 2 (SVCT-2) in human breast cancer cells. Treatment of human breast cancer cells with L-ascorbate differentially induced cell death, dependent on the SVCT-2 protein level. Moreover, knockdown of endogenous SVCT-2 via RNA interference in breast cancer cells expressing high levels of the protein induced resistance to L-ascorbate treatment, whereas transfection with SVCT-2 expression plasmids led to enhanced L-ascorbate chemosensitivity. Surprisingly, tumor regression by L-ascorbate administration in mice bearing tumor cell xenograft also corresponded to the SVCT-2 protein level. Interestingly, SVCT-2 expression was absent or weak in normal tissues, but strongly detected in tumor samples obtained from breast cancer patients. In addition, enhanced chemosensitivity to L-ascorbate occurred as a result of caspase-independent autophagy, which was mediated by beclin-1 and LC3 II. In addition, treatment with N-acetyl-L-cysteine, a reactive oxygen species (ROS) scavenger, suppressed the induction of beclin-1 and LC3 II, implying that the differential SVCT-2 protein-dependent L-ascorbate uptake was attributable to intracellular ROS induced by L-ascorbate, subsequently leading to autophagy. These results suggest that functional SVCT-2 sensitizes breast cancer cells to autophagic damage by increasing the L-ascorbate concentration and intracellular ROS production and furthermore, SVCT-2 in breast cancer may act as an indicator for commencing L-ascorbate treatment.

Topics: Acetylcysteine; Animals; Ascorbic Acid; Autophagy; Breast Neoplasms; Cell Line, Tumor; Female; Humans; Mice; Mice, Inbred BALB C; Reactive Oxygen Species; Sodium-Coupled Vitamin C Transporters

Degradation of the extracellular matrix (ECM) plays a critical role in the formation of tumors and metastasis and has been found to correlate with the aggressiveness of tumor growth and invasiveness of cancer. Ascorbic acid, which is known to be essential for the structural integrity of the intercellular matrix, is not produced by humans and must be obtained from the diet. Cancer patients have been shown to have very low reserves of ascorbic acid. Our main objective was to determine the effect of ascorbate supplementation on metastasis, tumor growth and tumor immunohistochemistry in mice unable to synthesize ascorbic acid [gulonolactone oxidase (gulo) knockout (KO)] when challenged with B16FO melanoma or 4T1 breast cancer cells. Gulo KO female mice 36-38 weeks of age were deprived of or maintained on ascorbate in food and water for 4 weeks prior to and 2 weeks post intraperitoneal (IP) injection of 5x105 B16FO murine melanoma cells or to injection of 5x105 4T1 breast cancer cells into the mammary pad of mice. Ascorbate-supplemented gulo KO mice injected with B16FO melanoma cells demonstrated significant reduction (by 71%, p=0.005) in tumor metastasis compared to gulo KO mice on the control diet. The mean tumor weight in ascorbate supplemented mice injected with 4T1 cells was reduced by 28% compared to tumor weight in scorbutic mice. Scorbutic tumors demonstrated large dark cores, associated with increased necrotic areas and breaches to the tumor surface, apoptosis and matrix metalloproteinase-9 (MMP-9), and weak, disorganized or missing collagen I tumor capsule. In contrast, the ascorbate-supplemented group tumors had smaller fainter colored cores and confined areas of necrosis/apoptosis with no breaches from the core to the outside of the tumor and a robust collagen I tumor capsule. In both studies, ascorbate supplementation of gulo KO mice resulted in profoundly decreased serum inflammatory cytokine interleukin (IL)-6 (99% decrease, p=0.01 in the B16F0 study and 85% decrease, p=0.08 in the 4T1 study) compared to the levels in gulo KO mice deprived of ascorbate. In the B16FO study, ascorbate supplementation of gulo KO mice resulted in profoundly de

Topics: Animals; Antioxidants; Apoptosis; Ascorbic Acid; Ascorbic Acid Deficiency; Breast Neoplasms; Cell Proliferation; Dietary Supplements; Female; Humans; Immunoenzyme Techniques; L-Gulonolactone Oxidase; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Melanoma, Experimental; Mice; Mice, Inbred BALB C; Mice, Knockout; Neoplasm Metastasis; Tumor Cells, Cultured; Vascular Endothelial Growth Factor A

There is concern that antioxidant supplement use during chemotherapy and radiation therapy may decrease treatment effects, yet the effects of such supplements on recurrence and survival are largely unknown.. The authors prospectively examined the associations between antioxidant use after breast cancer (BC) diagnosis and BC outcomes in 2264 women in the Life After Cancer Epidemiology (LACE) cohort. The cohort included women who were diagnosed with early stage, primary BC from 1997 to 2000 who enrolled, on average, 2 years postdiagnosis. Baseline data were collected on antioxidant supplement use since diagnosis and other factors. BC recurrence and mortality were ascertained, and hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using delayed entry Cox proportional hazards models. All tests of statistical significance were 2-sided.. Antioxidant supplement use after diagnosis was reported by 81% of women. Among antioxidant users, frequent use of vitamin C and vitamin E was associated with a decreased risk of BC recurrence (vitamin C: HR, 0.73; 95% CI, 0.55-0.97; vitamin E: HR, 0.71; 95% CI, 0.54-0.94); and vitamin E use was associated with a decreased risk of all-cause mortality (HR, 0.76; 95% CI, 0.58-1.00). Conversely, frequent use of combination carotenoids was associated with increased risk of death from BC (HR, 2.07; 95% CI, 1.21-3.56) and all-cause mortality (HR, 1.75; 95% CI, 1.13-2.71).. Frequent use of vitamin C and vitamin E in the period after BC diagnosis was associated with a decreased likelihood of recurrence, whereas frequent use of combination carotenoids was associated with increased mortality. The effects of antioxidant supplement use after diagnosis likely differ by type of antioxidant.

Topics: Adult; Aged; Antioxidants; Ascorbic Acid; Breast Neoplasms; Carotenoids; Cohort Studies; Dietary Supplements; Female; Humans; Middle Aged; Neoplasm Recurrence, Local; Treatment Outcome; Vitamin E

Vitamin C intake has been inversely associated with breast cancer risk in case-control studies, but not in meta-analyses of cohort studies using Food Frequency Questionnaires, which can over-report fruit and vegetable intake, the main source of vitamin C. This is the first study to investigate associations between vitamin C intake and breast cancer risk using food diaries.. Estimated dietary vitamin C intake was derived from 4-7 day food diaries pooled from five prospective studies in the UK Dietary Cohort Consortium. This nested case-control study of 707 incident breast cancer cases and 2144 matched controls examined breast cancer risk in relation to dietary vitamin C intake using conditional logistic regression adjusting for relevant covariates. Additionally, total vitamin C intake from supplements and diet was analysed in three cohorts.. No evidence of associations was observed between breast cancer risk and vitamin C intake analysed for dietary vitamin C intake (odds ratios (OR)=0.98 per 60 mg/day, 95% confidence interval (CI): 0.88-1.09, P (trend)=0.7), dietary vitamin C density (OR=0.97 per 60 mg/day, 95% CI: 0.87-1.07, P (trend)=0.5 ) or total vitamin C intake (OR=1.01 per 60 mg/day, 95% CI: 0.99-1.03, P (trend)=0.3). Additionally, there was no significant association for post-menopausal women (OR=1.02 per 60 mg/day, 95% CI: 0.99-1.05, P (trend)=0.3).. This pooled analysis of individual UK women found no evidence of significant associations between breast cancer incidence and dietary or total vitamin C intake derived uniquely from detailed diary recordings.

Topics: Aged; Ascorbic Acid; Breast Neoplasms; Case-Control Studies; Diet; Diet Records; Energy Intake; Female; Humans; Logistic Models; Middle Aged; Nutrition Assessment; Odds Ratio; Postmenopause; Prospective Studies; Risk Factors; United Kingdom

This is an observational study and the aim is to evaluate the effect of dietary supplements based on Resveratrol, Lycopene, Vitamin C and Anthocyanins (Ixor®) in reducing skin toxicity due to external beam radiotherapy in patients affected by breast cancer.. 71 patients were enrolled and they were divided in two different groups: a control group (CG) of 41 patients treated with prophylactic topical therapy based on hyaluronic acid and topical steroid therapy in case of occurrence of radiodermatitis, and a Ixor-Group (IG) of 30 patients treated also with an oral therapy based on Resveratrol, Lycopene, Vitamin C and Anthocyanin (Ixor®) at a dose of 2 tablets/day, starting from 10 days before the radiation treatment until 10 days after the end of treatment. Skin toxicity has been related to PTV, to breast volume that received a radiation dose equal or lower than 107%, included between 107% and 110%, or greater than 110% of the prescribed dose. Moreover it's been studied the relationship between skin toxicity and the chemotherapy schedule used before treatment. We calculated in both groups the percentage of patients who had a skin toxicity of grade 2 or 3 (according to RTOG scale). Absolute risk reduction (ARR), relative risk (RR) and odds ratio (OR) have been calculated for each relationship.. Control Group (CG) patients with a PTV > 500 ml presented skin toxicity G2 + G3 in 30% of cases, versus 25% of Ixor-Group (IG) [OR 0.77]. In patients with a PTV < 500 ml G2 + G3 toxicity was 0% in the IG compared to 18% in CG (OR 0.23). When Dmax was less than or equal to 107% of the prescribed dose skin toxicity was G2 + G3 in 12.5% in CG, versus 0% in IG (OR 0.73), instead when Dmax was included between 107 and 110% of the prescribed dose, G2 + G3 skin toxicity was 35% in CG and 21% in IG (OR 0.50). In patients undergoing chemotherapy with anthracyclines and taxanes, G2 + G3 toxicity was 27% in CG, against 20% in IG (OR 0.68).. The protective effect of Resveratrol, Lycopene, Vitamin C and Anthocyanin (Ixor®) is more detected in patients with PTV < 500 ml, when Dmax reaches values lower or equal to 107%, but not exceeding 110% of the prescribed dose, and in patients undergoing adjuvant chemotherapy with anthracyclines and taxanes.

Topics: Adult; Aged; Aged, 80 and over; Anthocyanins; Antioxidants; Ascorbic Acid; Breast Neoplasms; Carotenoids; Female; Humans; Lycopene; Middle Aged; Prognosis; Radiation-Protective Agents; Radiodermatitis; Radiotherapy, Conformal; Resveratrol; Stilbenes; Vitamins

In vitro antiproliferative effects of selenium nanoparticles (nanoSe(0), 10-40 μmol/L) on HeLa (human cervical carcinoma) cells and MDA-MB-231 (human breast carcinoma) cells were examined by optical microscopic inspection and MTT assay in the present study. The nanoSe(0) effectively inhibited the growth of MDA-MB-231 cells and HeLa cells in a dose-dependent manner. The morphology analysis with atomic force microscope showed that the HeLa cells treated with 10 μmol/L nanoSe(0) were rough and shrunken with truncated lamellipodia at terminal part of the cells. Flow cytometric analysis demonstrated that HeLa cells were arrested at S phase of the cell cycle after exposed to nanoSe(0) (10 μmol/L). Taken together, our results suggested that nanoSe(0) may be more helpful in cancer chemoprevention as a potential anticancer drug.

Topics: Anticarcinogenic Agents; Apoptosis; Ascorbic Acid; Breast Neoplasms; Carcinoma; Cell Line, Tumor; Cell Proliferation; Cell Survival; Dose-Response Relationship, Drug; Female; Flow Cytometry; HeLa Cells; Humans; Microscopy, Atomic Force; Nanoparticles; S Phase; Selenium Compounds; Selenium Oxides; Uterine Cervical Neoplasms

Ascorbic acid demonstrates a cytotoxic effect by generating hydrogen peroxide, a reactive oxygen species (ROS) involved in oxidative cell stress. A panel of eleven human cancer cell lines, glioblastoma and carcinoma, were exposed to serial dilutions of ascorbic acid (5-100 mmol/L). The purpose of this study was to analyse the impact of catalase, an important hydrogen peroxide-detoxifying enzyme, on the resistance of cancer cells to ascorbic acid mediated oxidative stress.. Effective concentration (EC(50)) values, which indicate the concentration of ascorbic acid that reduced the number of viable cells by 50%, were detected with the crystal violet assay. The level of intracellular catalase protein and enzyme activity was determined. Expression of catalase was silenced by catalase-specific short hairpin RNA (sh-RNA) in BT-20 breast carcinoma cells. Oxidative cell stress induced apoptosis was measured by a caspase luminescent assay.. The tested human cancer cell lines demonstrated obvious differences in their resistance to ascorbic acid mediated oxidative cell stress. Forty-five percent of the cell lines had an EC(50) > 20 mmol/L and fifty-five percent had an EC(50) < 20 mmol/L. With an EC(50) of 2.6-5.5 mmol/L, glioblastoma cells were the most susceptible cancer cell lines analysed in this study. A correlation between catalase activity and the susceptibility to ascorbic acid was observed. To study the possible protective role of catalase on the resistance of cancer cells to oxidative cell stress, the expression of catalase in the breast carcinoma cell line BT-20, which cells were highly resistant to the exposure to ascorbic acid (EC(50): 94,9 mmol/L), was silenced with specific sh-RNA. The effect was that catalase-silenced BT-20 cells (BT-20 KD-CAT) became more susceptible to high concentrations of ascorbic acid (50 and 100 mmol/L).. Fifty-five percent of the human cancer cell lines tested were unable to protect themselves against oxidative stress mediated by ascorbic acid induced hydrogen peroxide production. The antioxidative enzyme catalase is important to protect cancer cells against cytotoxic hydrogen peroxide. Silenced catalase expression increased the susceptibility of the formerly resistant cancer cell line BT-20 to oxidative stress.

Topics: Antineoplastic Agents; Antioxidants; Apoptosis; Ascorbic Acid; Breast Neoplasms; Carcinoma; Catalase; Cell Line, Tumor; Gene Silencing; Glioblastoma; Humans; Hydrogen Peroxide; Neoplasms; Oxidants; Oxidative Stress; RNA, Small Interfering; Vitamins

Topics: Ascorbic Acid; Breast Neoplasms; Clinical Trials as Topic; Female; Germany; Humans; Infusions, Intravenous; Orthomolecular Therapy; Treatment Outcome

Epidemiological data and studies in rodent models strongly support the role of estrogens in the development of breast cancers. Oxidative stress has been implicated in this carcinogenic process. We have recently demonstrated that antioxidants vitamin C or butylated hydroxyanisole (BHA) severely inhibit 17β-estradiol (E2)-induced breast tumor development in female ACI rats. The objective of this study was to characterize the mechanism of antioxidant-mediated prevention of breast cancer. Female August Copenhagen Irish (ACI) rats were treated with E2, vitamin C, vitamin C + E2, BHA and BHA + E2 for up to 8 months. Superoxide dismutase 3 (SOD3) was suppressed in E2-exposed mammary tissues and in mammary tumors of rats treated with E2. This suppression was overcome by co-treatment of rats with E2 and vitamin C or BHA. 8-Hydroxydeoxyguanosine (8-OHdG) levels determined as a marker of oxidative DNA damage were higher in E2-exposed mammary tissues and in mammary tumors compared with age-matched controls. Vitamin C or BHA treatment significantly decreased E2-mediated increase in 8-OHdG levels in the mammary tissues and in MCF-10A cells. Increased DNA damage, colony and mammosphere formation, and migration in SOD3 knocked down MCF-10A cells, and nuclear translocation of SOD3 in vitamin C-treated mammary tissues and in MCF-10A cells suggest protective role of SOD3 against DNA damage and mammary carcinogenesis. Our studies further demonstrate that SOD3, but not SOD2 and SOD1, is induced by antioxidants and is regulated through NRF2. SOD3 may thus be an important gene in defense against oxidative stress and in the prevention of estrogen-mediated breast cancer.

Topics: Active Transport, Cell Nucleus; Antioxidants; Ascorbic Acid; Breast Neoplasms; Butylated Hydroxyanisole; Cell Line, Tumor; DNA Damage; Estradiol; Female; Gene Expression Regulation, Enzymologic; Humans; NF-E2-Related Factor 2; RNA, Messenger; Superoxide Dismutase; Superoxide Dismutase-1

To determine whether frequent vitamin C supplement use is associated with healthier behaviours, and a history of cancer and other illnesses in UK women.. The present cross-sectional analysis examines the odds of taking supplements containing vitamin C as recorded in 4 d food diaries, based on lifestyle characteristics and morbidity history self-reported by questionnaire.. A large national UK cohort study.. A total of 12,453 women aged between 37 and 79 years.. Women frequently taking supplements containing vitamin C, compared to those who did not, had healthier behaviours, including higher consumption of fruit and vegetables. Frequent high-dose vitamin C users (≥1000 mg) had a higher socio-economic status, visited alternative practitioners more often than family or private doctors, and were more likely to be ex-smokers and to drink little or no alcohol. Women who self-reported having had cancer (OR = 1·33, 95% CI 1·00, 1·76) or specifically breast cancer (OR = 1·70, 95% CI 1·14, 2·55), or reported a family history of cancer (OR = 1·16, 95% CI 0·95, 1·41) or breast cancer (OR = 1·26, 95% CI 1·01, 1·58) had increased odds of being frequent high-dose users after adjusting for sociodemographic and health behaviours. Women with personal or family histories of some cardiovascular or intestinal disorders were more likely to take supplements containing vitamin C, though not necessarily at high doses.. High-dose vitamin C intake by UK women was associated with healthier behaviours and a history of breast cancer, total cancer and other illnesses. Consequences of high-dose vitamin C supplement intake are not clear at the population level.

Topics: Adult; Aged; Antioxidants; Ascorbic Acid; Breast Neoplasms; Cardiovascular Diseases; Cohort Studies; Cross-Sectional Studies; Diet Records; Dietary Supplements; Dose-Response Relationship, Drug; Female; Health Behavior; Humans; Life Style; Middle Aged; Odds Ratio; Socioeconomic Factors; United Kingdom

This study was conducted to evaluate blood concentrations of inflammatory cytokines and oxidative stress-related biomarkers as risk factors of breast cancer and to determine the relation between these markers and antioxidant nutrient intake.. Study subjects were 134 patients with breast cancer and 149 controls. Total antioxidant capacity and concentrations of 8-isoprostane, 8-hydroxy-2'-deoxyguanosine, interleukin (IL)-1β, IL-6, and IL-8 of blood samples were determined. A food-frequency questionnaire was used to assess nutrient intake.. Patients with breast cancer had significantly higher blood levels of oxidative stress markers compared with control subjects. Plasma concentrations of IL-1β and IL-6 were significantly higher in patients with breast cancer compared with those of control subjects. In the pooled analysis, total antioxidant capacity was significantly decreased with increasing quartiles of carbohydrate intake but was increased with increasing quartiles of total vitamin A intake and vitamin C intake. In addition, 8-hydroxy-2'-deoxyguanosine concentration was decreased with increasing quartiles of vitamin A and β-carotene. No significant association was found between nutrient intake and cytokine concentrations.. These results suggest that oxidative stress and inflammation may be associated with the risk of breast cancer. Total vitamin A intake was negatively related to oxidative stresses, possibly modifying the risk of breast cancer.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Antioxidants; Ascorbic Acid; beta Carotene; Biomarkers; Breast Neoplasms; Case-Control Studies; Deoxyguanosine; Diet; Diet Surveys; Dietary Carbohydrates; Female; Humans; Inflammation; Inflammation Mediators; Interleukin-1beta; Interleukin-6; Middle Aged; Oxidative Stress; Risk Factors; Surveys and Questionnaires; Vitamin A; Vitamins

So far, studies on dietary antioxidant intake, including beta-carotene, vitamin C and vitamin E, and breast cancer risk are inconclusive. Thus, we addressed this question in the European Prospective Investigation into Cancer and Nutrition. During a median follow-up time of 8.8 years, 7,502 primary invasive breast cancer cases were identified. Cox proportional hazard models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI). All analyses were run stratified by menopausal status at recruitment and, additionally, by smoking status, alcohol intake, use of exogenous hormones and use of dietary supplements. In the multivariate analyses, dietary intake of beta-carotene, vitamin C and E was not associated with breast cancer risk in premenopausal [highest vs. lowest quintile: HR, 1.04 (95% CI, 0.85-1.27), 1.12 (0.92-1.36) and 1.11 (0.84-1.46), respectively] and postmenopausal women [0.93 (0.82-1.04), 0.98 (0.87-1.11) and 0.92 (0.77-1.11), respectively]. However, in postmenopausal women using exogenous hormones, high intake of beta-carotene [highest vs. lowest quintile; HR 0.79 (95% CI, 0.66-0.96), P (trend) 0.06] and vitamin C [0.88 (0.72-1.07), P (trend) 0.05] was associated with reduced breast cancer risk. In addition, dietary beta-carotene was associated with a decreased risk in postmenopausal women with high alcohol intake. Overall, dietary intake of beta-carotene, vitamin C and E was not related to breast cancer risk in neither pre- nor postmenopausal women. However, in subgroups of postmenopausal women, a weak protective effect between beta-carotene and vitamin E from food and breast cancer risk cannot be excluded.

Topics: Adult; Aged; Antioxidants; Ascorbic Acid; beta Carotene; Breast Neoplasms; Diet; Europe; Female; Humans; Middle Aged; Postmenopause; Premenopause; Proportional Hazards Models; Risk; Surveys and Questionnaires; Vitamin E

This study was carried out to determine the relationships between leptin concentrations, lipid alterations, oxidant/ antioxidant status, in vitro LDL oxidizability and LDL-fatty acid composition in overweight breast cancer patients. Glucose, insulin, leptin, lipids, LDL-cholesteryl ester fatty acids, markers of oxidant status (MDA, Hydroperoxides, carbonyl proteins, conjugated dienes) and markers of antioxidant status (vitamins A, C, E, erythrocyte activities of the enzymes superoxide dismutase, SOD, catalase, glutathione peroxidase,GPx, and glutathione reductase, GR and the serum total antioxidant status, ORAC) were investigated in breast cancer patients and in control women. Our findings showed that insulin, leptin, triglyceride, cholesterol and LDL-C concentrations were increased in patients compared to controls. ORAC and vitamin C and E values were lower while plasma hydroperoxide, carbonyl protein and conjugated diene levels, SOD and GPx activities were higher than in controls. Alterations in LDL-fatty acid composition were associated with their enhanced oxidative susceptibility. There were significant positive correlations between leptin concentrations and LDL-C, hydroperoxides, carbonyl proteins, SOD activity, baseline conjugated diene levels and oxidation rate, and significant negative correlations between leptin and ORAC, lag time and LDL-PUFA in patients. In conclusion, breast cancer is associated with lipid alterations and enhanced oxidative stress linked to high leptin levels in overweight.

Topics: Adult; Antioxidants; Ascorbic Acid; Body Mass Index; Breast Neoplasms; Catalase; Female; Glutathione Peroxidase; Glutathione Reductase; Humans; Leptin; Lipoproteins; Middle Aged; Neoplasm Staging; Overweight; Oxidative Stress; Superoxide Dismutase; Vitamin A; Vitamin E

During breast cancer metastasis to bone, tumor cells home to bone marrow, likely targeting the stem cell niche, and stimulate osteoclasts, which mediate osteolysis required for tumor expansion. Although osteoblasts contribute to the regulation of the hematopoietic stem cell niche and control osteoclastogenesis through production of proresorptive cytokine RANKL (receptor activator of NF-κB ligand), their role in cancer metastases to bone is not fully understood. C57BL/6J mouse bone marrow cells were treated for 3-12 days with ascorbic acid (50 μg/ml) in the presence or absence of 10% medium conditioned by breast carcinoma cells MDA-MB-231, 4T1, or MCF7. Treatment with cancer-derived factors resulted in a sustained 40-60% decrease in osteoblast differentiation markers, compared with treatment with ascorbic acid alone, and induced an osteoclastogenic change in the RANKL/osteoprotegerin ratio. Importantly, exposure of bone cells to breast cancer-derived factors stimulated the subsequent attachment of cancer cells to immature osteoblasts. Inhibition of γ-secretase using pharmacological inhibitors DAPT and Compound E completely reversed cancer-induced osteoclastogenesis as well as cancer-induced enhancement of cancer cell attachment, identifying γ-secretase activity as a key mediator of these effects. Thus, we have uncovered osteoblasts as critical intermediary of premetastatic signaling by breast cancer cells and pinpointed γ-secretase as a robust target for developing therapeutics potentially capable of reducing both homing and progression of cancer metastases to bone.

Topics: Amyloid Precursor Protein Secretases; Animals; Antigens, Differentiation; Antioxidants; Ascorbic Acid; Benzodiazepinones; Bone Marrow Cells; Bone Neoplasms; Breast Neoplasms; Cell Differentiation; Cell Line, Tumor; Culture Media, Conditioned; Female; Humans; Mammary Neoplasms, Animal; Mice; Neoplasm Metastasis; Osteoblasts; Osteoclasts; Osteoprotegerin; RANK Ligand; Signal Transduction

Few studies on micronutrients and postmenopausal breast cancer have examined the association with breast cancer characteristics. The aim of this study was to investigate the associations between vitamin C, vitamin E, folate and beta-carotene from diet and supplements and risk of postmenopausal breast cancer subtypes defined by histology (ductal/lobular), estrogen receptor (ER) and progesterone receptor (PGR) status. In a prospective cohort study of 26,224 postmenopausal women information on diet, supplements and lifestyle was collected through questionnaires. One thousand seventy-two cases were identified during follow-up. Incidence rate ratios of total breast cancers and breast cancer subtypes related to micronutrient intake were calculated using Cox proportional hazard analyses. This study found no association between overall breast cancer and any micronutrients, while some effects were shown when stratifying by breast cancer subtypes: dietary but not supplemental beta-carotene showed a protective effect against lobular breast cancer [incidence rate ratio (IRR): 0.72; 95% confidence interval (CI): 0.57-0.91]. Dietary vitamin E was associated with decreased risk of ER and PGR positive breast cancer (IRR: 0.50; 95% CI: 0.25-0.98) and dietary folate was associated with increased risk of ER and PGR positive breast cancer (IRR: 1.27; 95% CI: 1.03-1.95). This study found no effect of micronutrients on overall risk of postmenopausal breast cancer, but indicated possible effects of micronutrients in subgroups of breast cancer, with a potential beneficial effect of dietary beta-carotene in lobular breast cancer and dietary vitamin E in ER + PGR+ breast cancer and a potential harmful effect of dietary folate in ER+ PGR+ breast cancer.

Topics: Ascorbic Acid; beta Carotene; Breast Neoplasms; Diet; Dietary Supplements; Female; Folic Acid; Follow-Up Studies; Humans; Micronutrients; Middle Aged; Neoplasm Proteins; Postmenopause; Prospective Studies; Receptors, Estrogen; Receptors, Progesterone; Risk; Surveys and Questionnaires; Vitamin E

Vitamin C is a water-soluble chain-breaking antioxidant that has beneficial effects on lipid-metabolizing enzymes. In the present study, the level of thiobarbituric acid (TBA) substances and antioxidant enzymes such as catalase, superoxide dismutase (SOD), glutathione peroxidase and glutathione-S-transferase were assayed.. The level of TBA substances and antioxidant enzymes was determined in plasma and RBC hemolysates, respectively, in 60 postmenopausal women with breast cancer.. The data obtained from the study revealed that the levels of TBA and the antioxidant enzymes catalase, SOD, glutathine peroxidase and glutathine-S-transferse were significantly normalized by vitamin C treatment in the RBC hemolysate.. The results compared vitamin C-treated breast cancer patients with normal individuals and showed that co-administration of vitamin C is more beneficial in breast cancer patients treated with tamoxifen.

Topics: Antineoplastic Agents, Hormonal; Antioxidants; Ascorbic Acid; Breast Neoplasms; Catalase; Erythrocytes; Female; Glutathione; Glutathione Peroxidase; Glutathione Transferase; Humans; Lipid Peroxidation; Oxidative Stress; Superoxide Dismutase; Tamoxifen; Thiobarbiturates; Vitamin E; Vitamins

Berries and berry extracts possess properties that make them important in the prevention of cancer. The high antioxidant levels of these extracts play a role, but components of the berries can have other effects on cell replication and survival. We chose to test the hypothesis that (i) although the antioxidant capacity of raspberry extracts is important for inhibiting the proliferation of tumor cells, other characteristics of the berry extracts are responsible for a major part of their antiproliferative activity, and that (ii) the relative importance of the antioxidant effect can depend on the cell type being studied. The aim of this study was to assess the relative roles of low pH and high antioxidant levels in the killing of 3 cell types by an aqueous extract from Meeker red raspberries. Stomach, colon, and breast cancer cells were treated with berry extract and with HCl and ascorbic acid solutions of the same pH. A dilution of 7.5% ascorbic acid solution, of the same pH and slightly higher antioxidant concentration than the berry extract, killed less than 10% of the stomach and colon cancer cells. In contrast, the berry extract at this same dilution killed more than 90% of these cells. Antioxidants played a more significant role in the killing of breast cancer cells, however. For these cells, approximately 50% of the killing could be attributed to antioxidant effects. We conclude that the antioxidant effect plays a minor role in the killing of 2 gastrointestinal cell types, but its role in inactivating a breast cancer cell line is much more significant. No evidence of apoptosis was observed, and caspase activation did not contribute to cell killing by the extract.

Topics: Adenocarcinoma; Antioxidants; Ascorbic Acid; Breast Neoplasms; Caspases; Cell Division; Cell Line, Tumor; Colonic Neoplasms; Fruit; Humans; Phytotherapy; Plant Extracts; Stomach Neoplasms

The effects of dietary intake of antioxidant vitamins on breast cancer risk are inconclusive. Moreover, little is known as to whether associations differ between non-Hispanic White (NHW) and Hispanic women. We assessed the associations of the dietary intake of antioxidant vitamins commonly found in fruits and vegetables with breast cancer risk and estrogen receptor (ER) status among NHW and Hispanic women living in the Southwestern U.S.. Primary breast cancer cases in the 4-Corners region (Arizona, Colorado, New Mexico, Utah), diagnosed between October 1999 and May 2004, were identified through state cancer registries. Controls were frequency matched by ethnicity and age (+/-5 years). Information on demographic characteristics and other breast cancer risk factors prior to the referent year were collected by interviewer-administered computerized questionnaire. A modified extensive diet history questionnaire was used to assess dietary intake.. We did not find a protective effect of dietary antioxidants, such as alpha or beta-carotene, beta-cryptoxanthin, lutein/zeaxanthin, lycopene, retinol, vitamin C, alpha, delta, beta or gamma-tocopherol, on breast cancer risk in populations living in the Southwest. We did not find any consistent associations with multivariate risk of breast cancer or estrogen receptor status. Cigarette smoking was not a significant effect modifier of these associations.. This case-control study did not find any meaningful association of the dietary intake of antioxidant vitamins with breast cancer risk or ER status.

Topics: Adult; Aged; Antioxidants; Ascorbic Acid; Body Mass Index; Breast Neoplasms; Carotenoids; Case-Control Studies; Diet; Diet Records; Female; Hispanic or Latino; Humans; Middle Aged; Motor Activity; Receptors, Estrogen; Risk Factors; Southwestern United States; Tocopherols; Vitamin A; White People

The influence of vitamin supplements on breast cancer risk is unclear and the interactive effects of dietary and supplemental sources are unknown. This study investigated (1) the association between self-reported vitamin supplement use (multivitamin, A, B, C, and E) and breast cancer and (2) the combined effect of vitamin supplements in relation to dietary vitamin intakes on breast cancer risk.. The Shanghai Breast Cancer Study was a population-based case-control study conducted in Shanghai in 1996-1998 (Phase I) and 2002-2004 (Phase II). Participants were aged 25-64 (Phase I) and 20-70 years (Phase II). The analyses included 3,454 incident breast cancer cases and 3,474 controls. Unconditional logistic regression models were used to determine adjusted odds ratios (ORs) for breast cancer risk associated with vitamin supplement use.. Overall, breast cancer risk was not related to any vitamin supplement intake. However, a 20% reduction in breast cancer risk was observed with vitamin E supplement use among women with low-dietary vitamin E intake (OR = 0.8; 95% confidence interval (CI), 0.6-1.0). A non-significant 20% risk reduction was observed among vitamin B supplement users with low B dietary intake (OR = 0.8; 95% CI, 0.6-1.1). Frequent use of a vitamin B supplement was adversely associated with breast cancer risk among those with high dietary vitamin B intake (OR = 1.4; 95% CI: 0.9-2.1; P for interaction = 0.07).. This study suggests that vitamins E and B supplements may confer protection against breast cancer among women who have low dietary intake of those vitamins.

Topics: Adult; Aged; Ascorbic Acid; Breast Neoplasms; Case-Control Studies; Dietary Supplements; Female; Humans; Middle Aged; Risk; Vitamin A; Vitamin B Complex; Vitamin E; Vitamins

Few studies have evaluated carotenoids and vitamins C and E in association with the risk of breast cancers defined by estrogen receptor (ER) and progesterone receptor (PR) status.. We examined the associations between dietary and supplemental intakes of these nutrients and risk of breast cancers jointly defined by both ER and PR status among postmenopausal women.. Our investigation was conducted in the Women's Health Initiative Observational Study. After following 84 805 women for an average of 7.6 y, 2879 incident invasive breast cancer cases had been ascertained, of whom 2509 had receptor data. We used Cox proportional hazards models to assess the associations of interest.. Dietary alpha-carotene (highest versus lowest quintile: RR = 0.83; 95% CL = 0.70, 0.99; P for trend = 0.019), beta-carotene (highest versus lowest quintile: RR = 0.78; 95% CL = 0.66, 0.94; P for trend = 0.021), and lycopene (highest versus lowest quintile: RR = 0.85; 95% CL = 0.73, 1.00; P for trend = 0.064) were inversely associated with risk of ER+PR+breast cancer, but not with other breast cancer groups jointly defined by ER and PR status. Total or supplemental beta-carotene and dietary intakes of lutein+zeaxanthin and beta-cryptoxanthin were not associated with breast cancers defined by ER and PR status. Vitamin E (regardless of source) and dietary vitamin C were not associated with breast cancer. However, total and supplemental vitamin C intake had weak positive associations with breast cancer overall.. Dietary intake of certain carotenoids might be differentially associated with risk of invasive breast cancers jointly defined by ER and PR status among postmenopausal women.

Topics: Aged; Antioxidants; Ascorbic Acid; Breast Neoplasms; Carotenoids; Cohort Studies; Diet; Diet Surveys; Dietary Supplements; Female; Follow-Up Studies; Humans; Middle Aged; Postmenopause; Proportional Hazards Models; Prospective Studies; Receptors, Estrogen; Receptors, Progesterone; United States; Vitamin E

Catalytic therapy (CT) is a cancer treatment modality based on the generation of reactive oxygen species (ROS) using a combination of substrate molecules and a catalyst. The most frequently used substrate and catalyst pair is ascorbate/Co phthalocyanine (PcCo). In the present study, porphyrins containing transition metal ions as catalysts in place of PcCo were studied. Porphyrins that are expected to be as efficient as phthalocyanines, but may have fewer side effects, were analyzed. ROS production through the combined use of ascorbate and porphyrins decreased the number of breast cancer tumor cells by 20-40% after a single in vitro treatment, as compared to control cells. Treatment with ascorbate in conjunction with porphyrins stimulated apoptosis and disrupted the cell cycle. These treatments enhanced apoptosis by 20-40% when compared to treatments with ascorbate and porphyrins. In addition, the number of cells accumulating in the sub G0/G1 stage of the cell cycle increased from 3- to 10-fold, potentially reflecting that the treatment was highly effective in inducing DNA damage in the tumor cells, suggesting that porphyrins may be beneficial as a CT catalyst in the treatment of cancer.

Topics: Animals; Ascorbic Acid; Breast Neoplasms; Catalysis; Cell Line, Tumor; Humans; Melanoma, Experimental; Mice; Porphyrins; Reactive Oxygen Species

Tamoxifen (TAM) is a non-steroidal anti-estrogen used widely in the treatment and chemoprevention of breast cancer. TAM treatment can lead to DNA damage, but the mechanism of this process is not fully understood and the experimental data are often inconclusive. We compared the DNA-damaging potential of TAM in normal human peripheral blood lymphocytes and MCF-7 breast cancer cells by using the comet assay. In order to assess whether oxidative DNA damage may contribute to TAM-induced lesions, we employed two DNA repair enzymes: endonuclease III (Endo III) and formamidopyrimidine-DNA glycosylase (Fpg). The kinetics of repair of DNA damage was also measured. In order to evaluate the involvement of free radicals in the genotoxicity of TAM we pre-treated the cells with nitrone spin traps: DMPO and POBN. The use of common antioxidants: vitamin C, amifostine and genistein, helped to assess the contribution of free radicals. TAM damaged DNA in both normal and cancer cells, inducing mainly DNA strand breaks but not alkali-labile sites. The drug at 5 and 10 microM induced DNA double strand breaks (DSBs) in lymphocytes and at 10 microM in MCF-7 cells. We observed complete repair of DSBs in cancer cells by contrast with incomplete repair of these lesions in lymphocytes. In both types of cells TAM induced oxidized purines and pyrimidines. Incubation of the cells with nitrone spin traps and antioxidants decreased, with exception of amifostine in MCF-7 cells, the extents of DNA damage in both kinds of cells, but the results were more distinct in cancer cells. Our results indicate that TAM can be genotoxic for normal and cancer cells by free radicals generation. It seems to have a higher genotoxic potential for normal cells, which can be the result of incomplete repair of DNA DSBs. Free radicals scavengers can modulate TAM-induced DNA damage interfering with its antitumour activity in cancer cells.

Topics: Adult; Amifostine; Ascorbic Acid; Breast Neoplasms; Cell Line, Tumor; Cell Survival; Comet Assay; DNA; DNA Breaks, Double-Stranded; DNA Breaks, Single-Stranded; DNA Damage; DNA Repair; DNA-Formamidopyrimidine Glycosylase; Dose-Response Relationship, Drug; Endodeoxyribonucleases; Estrogen Receptor Modulators; Female; Free Radical Scavengers; Genistein; Humans; Hydrogen-Ion Concentration; Kinetics; Lymphocytes; Male; Mutagens; Oxidative Stress; Reactive Oxygen Species; Tamoxifen

Cancer is associated with increased cell growth, and expression of matrix metalloproteinases (MMPs) and transforming growth factor-beta (TGF-beta). The dose-dependent effects of ascorbate (Vitamin C) on cancer cell growth, and expression of MMPs and TGF-beta were examined. Renal-adenocarcinoma, melanoma and mammary cancer cells were dosed with 0-100mM ascorbate and examined for cell survival or proliferation, and expression of MMP-1, MMP-2 and TGF-beta at protein and/or mRNA levels. The lower concentrations of ascorbate significantly inhibited cancer cell viability while stimulating MMPs and TGF-beta expression, indicating elimination of cancer cells with damage to the extracellular matrix (ECM). Conversely, ascorbate at higher concentrations dramatically stimulated cell proliferation and inhibited MMPs and TGF-beta expression, implicating growth and ECM advantage.

Topics: Adenocarcinoma; Antioxidants; Ascorbic Acid; Breast Neoplasms; Cell Survival; Enzyme-Linked Immunosorbent Assay; Extracellular Matrix; Humans; Kidney Neoplasms; Matrix Metalloproteinase 1; Matrix Metalloproteinase 2; Melanoma; RNA, Messenger; Skin Neoplasms; Transforming Growth Factor beta1; Tumor Cells, Cultured

The tropical ginger compound, 1'-acetoxychavicol acetate (ACA) possesses cancer chemopreventive properties in several models but its effects on breast cancer have not been fully evaluated. In this study, the effects of ACA on human breast carcinoma-derived MCF-7 and MDA-MB-231 cell viability were assessed using trypan blue exclusion analysis. ACA significantly decreased cell viability in a time- and dose-dependent manner, with effective concentrations 10-50 microM. Apoptosis was confirmed by morphological examination of cells through light microscopy, 4,6-diamidino-2-phenylindole dihydrochloride staining, and annexin V/Alexa Fluor 488 staining visualized using flow cytometry. ACA also increased protein expression of the activated form of caspase-3 in MDA-MB-231 cells. Addition of antioxidants N-acetylcysteine, ascorbic acid, or trolox prevented the loss of viability caused by ACA using trypan blue uptake as a marker. These results suggest ACA may have potential anticancer effects against breast carcinoma cells by inducing apoptosis.

Topics: Acetylcysteine; Antineoplastic Agents, Phytogenic; Antioxidants; Apoptosis; Ascorbic Acid; Benzyl Alcohols; Breast Neoplasms; Caspase 3; Cell Cycle; Cell Line, Tumor; Cell Survival; Chromans; Dose-Response Relationship, Drug; Enzyme Induction; Female; Humans; Terpenes; Time Factors

Although ascorbate (Vitamin C) has been shown to inhibit cell growth and induce cell death in variety of cancer cells, results reported in other studies are inconsistent with this conclusion. It was previously reported that ascorbate induces apoptosis in human breast cancer cells. However, the molecular mechanism for this is not clear. In this study, we demonstrate that ascorbate induces cell death through the apoptosis-inducing factor (AIF) in the human breast cancer cell lines, SK-BR3 and Hs578T, but not in a normal breast cell line, Hs578. Ascorbate treatment caused the nuclear translocation of AIF, which is retained in the mitochondria in healthy cells, but caspase cleavage is not induced. Moreover, MG132, an inhibitor of AIF release from mitochondria, blocked the induction of cell death. Furthermore, cells that had been treated with human AIF-specific siRNA resisted cell death induced by ascorbate, implying that the translocation of AIF from mitochondria to the nucleus is responsible for ascorbate-mediated cell death. Therefore, these results suggest that ascorbate activates a caspase-independent and AIF-mediated cell death pathway in human breast cancer cells, SK-BR3, and Hs578T.

Topics: Antineoplastic Agents; Antioxidants; Apoptosis; Apoptosis Inducing Factor; Ascorbic Acid; Breast Neoplasms; Caspase Inhibitors; Caspases; Cell Nucleus; Fluorescent Antibody Technique; Humans; Immunoblotting; Leupeptins; Mitochondria; Protein Transport; RNA, Small Interfering; Tumor Cells, Cultured

Breast cancer is an increasingly common malignancy. Several vitamins such as retinoic acid (RA), ascorbic acid (AA), vitamin D and vitamin E are known to prevent the development and progression of breast cancer.. We sought to determine whether RA and AA together (RA+AA) acted synergistically in blocking the proliferation of human breast cancer cells. To elucidate the mechanism by which RA+AA inhibited breast carcinoma proliferation, we then evaluated the gene expression profiles of the treated and untreated cells by radioactive cDNA microarray analysis.. We cultured the human breast cancer cell line MCF-7 for 3 days with 100 nM RA and/or 1 mM AA, counted the cell numbers and harvested the total RNAs for cDNA microarray analysis.. RA, AA and RA+AA reduced MCF-7 cell proliferation by 20.7%, 23.3% and 75.7% relative to the untreated cell proliferation, respectively. The synergistic ratio of RA and AA was 1.72. The MCF-7 gene expression profiles showed that 29 genes were up-regulated and 38 genes were down-regulated after RA+AA treatment. The nature of these genes suggests that the mechanism by which RA and AA act synergistically in inhibiting human breast cancer cell proliferation may involve the expression of genes that induce differentiation and block proliferation, and the up-regulation of antioxidant enzymes and proteins involved in apoptosis, cell cycle regulation and DNA repair.. Combined treatment with RA and AA inhibits the proliferation of human breast cancer cells by altering their gene expression related to antioxidation processes as well as the proliferation inhibitory pathway.

Topics: Antineoplastic Combined Chemotherapy Protocols; Ascorbic Acid; Breast Neoplasms; Cell Line, Tumor; Cell Proliferation; Drug Synergism; Female; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Oligonucleotide Array Sequence Analysis; Tretinoin

The effects of extracts from five cultivars of strawberries on the proliferation of colon cancer cells HT29 and breast cancer cells MCF-7 were investigated, and possible correlations with the levels of several antioxidants were analyzed. In addition, the effects of organic cultivation compared to conventional cultivation on the content of antioxidants in the strawberries and strawberry extracts on the cancer cell proliferation were investigated. The ratio of ascorbate to dehydroascorbate was significantly higher in the organically cultivated strawberries. The strawberry extracts decreased the proliferation of both HT29 cells and MCF-7 cells in a dose-dependent way. The inhibitory effect for the highest concentration of the extracts was in the range of 41-63% (average 53%) inhibition compared to controls for the HT29 cells and 26-56% (average 43%) for MCF-7 cells. The extracts from organically grown strawberries had a higher antiproliferative activity for both cell types at the highest concentration than the conventionally grown, and this might indicate a higher content of secondary metabolites with anticarcinogenic properties in the organically grown strawberries. For HT29 cells, there was a negative correlation at the highest extract concentration between the content of ascorbate or vitamin C and cancer cell proliferation, whereas for MCF-7 cells, a high ratio of ascorbate to dehydroascorbate correlated with a higher inhibition of cell proliferation at the second highest concentration. The significance of the effect of ascorbate on cancer cell proliferation might lie in a synergistic action with other compounds.

Topics: Antioxidants; Ascorbic Acid; Breast Neoplasms; Cell Division; Cell Line, Tumor; Food, Organic; Fragaria; Fruit; HT29 Cells; Humans; Neoplasms

Cellular iron is needed for cell survival and hydroxylation of hypoxia-inducible factor-1alpha (HIF-alpha) by prolyl hydroxylases (PHD). One mechanism of iron uptake is mediated by the cell surface transferrin receptor (TfR). Because iron is required for cell growth and suppression of HIF-alpha levels, we tested the effects of the two anti-TfR monoclonal antibodies (mAb) E2.3 and A27.15 on growth of breast cancer cells and induction of HIF-alpha and hypoxia-regulated genes. Treatment with both mAbs together synergistically inhibited cell proliferation in a dose-responsive manner by up to 80% following 8 days of exposure, up-regulated HIF-1alpha and HIF transcription targets, down-regulated TfR expression, and down-regulated cellular labile iron pool by 60%. Because combined treatment with anti-TfR mAbs resulted in the up-regulation of the hypoxia pathway, which may increase tumor angiogenesis, we analyzed the effects of ascorbate on cell viability and HIF-1alpha levels in cells treated with both anti-TfR mAbs together, as ascorbate has been shown to be required by PHD enzymes for full catalytic activity. Ascorbate at physiologic concentrations (25 micromol/L) suppressed HIF-1alpha protein levels and HIF transcriptional targets in anti-TfR mAb-treated cells but did not suppress the antiproliferative effect of the mAbs. These results indicate that the addition of ascorbate increased the activity of the PHD enzymes in down-regulating HIF but not the proliferation of iron-starved anti-TfR mAb-treated cells. The use of anti-TfR mAbs and ascorbate in inhibiting both cell proliferation and HIF-1alpha and angiogenesis under normoxic conditions may be of therapeutic use.

Topics: Antibodies, Monoclonal; Ascorbic Acid; Breast Neoplasms; Cell Growth Processes; Cell Line, Tumor; Cell Survival; Drug Synergism; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Iron; Receptors, Transferrin; Transcription, Genetic; Up-Regulation

Epirubicin fights cancer through topoisomerase II inhibition, hence producing DNA strand breaks that finally lead to cell apoptosis. But anthracyclines produce free radicals that may explain their adverse effects. Dexrazoxane--an iron chelator--was proven to decrease free radical production and anthracycline cardiotoxicity. In this article, we report the concentrations of cellular 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dGuo) relative to 2'-deoxyguanosine (dGuo), and comet assay results from a study including 20 cancer patients treated with epirubicin. Plasma concentrations of vitamins A, E, C and carotenoids are also reported. All data were obtained before and immediately after epirubicin infusion. The ratios of 8-Oxo-dGuo to dGuo were measured in leukocyte DNA by HPLC-coulometry after NaI extraction of nucleic acids. Vitamins A and E and carotenoids were measured by HPLC-spectrophotometry. Vitamin C was measured by HPLC-spectrofluorimetry. Median 8-oxo-dGuo/dGuo ratios increased significantly from 0.34 to 0.48 lesions per 100,000 bases while per cent of tail DNA increased from 3.47 to 3.94 after chemotherapy 8-Oxo-dGuo/dGuo and per cent of tail DNA medians remained in the normal range. Only vitamin C decreased significantly from 55.4 to 50.3 microM Decreases in vitamins A, E, lutein and zeaxanthin were not significant, but concentrations were below the lower limit of the normal range both before and after chemotherapy. Only the correlation between comet assay results and vitamin C concentrations was significant (rho =-0.517, p = 0.023). This study shows that cellular DNA is damaged by epirubicin-generated free radicals which produce the mutagenic modified base 8-oxo-dGuo and are responsible for strand breaks. However, strand breaks are created not only by free radicals but also by topoisomerase II inhibition. In a previous study we did not find any significant change in urinary 8-oxo-dGuo excretion after adriamycin treatment. However, 8-oxo-dGuo may have increased at the end of urine collection as DNA repair and subsequent kidney elimination are relatively slow processes. In another study, authors used GC-MS to detect 8-oxo-dGuo in DNA and did not find any change after prolonged adriamycin infusion. Reasons for these apparent discrepancies are discussed.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Aged; Antibiotics, Antineoplastic; Ascorbic Acid; Breast Neoplasms; Comet Assay; Deoxyguanosine; DNA Damage; Epirubicin; Female; Free Radicals; Humans; Leukocytes; Middle Aged; Vitamin A; Vitamin E

Oxidative stress resulting from an imbalance between pro-oxidants and anti-oxidants seems to play an important role in human breast carcinogenesis. There are conflicting reports regarding the tissue levels of malondialdehyde (MDA), ascorbic acid and superoxide dismutase (SOD) in breast cancer patients whereas few blood values have been reported. The present study was carried out to observe the changes in serum MDA, serum SOD and plasma ascorbic acid with the stage-wise progression of the disease. Serum MDA and serum SOD levels were found to be increased gradually from Stage I to Stage IV as compared to control group (p < 0.001). The maximum rise was in Stage IV patients. In contrast, mean plasma ascorbic acid levels were low in all stages compared to control group (p < 0.001). The decrease was more pronounced in Stage III and Stage IV. The study would be of immense help for establishing blood based biochemical marker in breast cancer patients.

Topics: Antioxidants; Ascorbic Acid; Breast Neoplasms; Case-Control Studies; Enzymes; Female; Humans; Lipid Peroxidation; Malondialdehyde; Neoplasm Staging; Reference Values; Superoxide Dismutase

Topics: Adult; Antioxidants; Ascorbic Acid; beta Carotene; Breast Neoplasms; Dietary Supplements; Female; Humans; Middle Aged; Neoplasms; Survival Rate; Survivors; Vitamin E

Hypoxia-inducible factor (HIF) plays an important role in determining patterns of gene expression in cancer. HIF is down-regulated in oxygenated cells by a series of Fe (II) and 2-oxoglutarate dependent dioxygenases that hydroxylate specific residues in the regulatory HIF-alpha subunits. Because these enzymes require ascorbate for activity in vitro we analyzed the effects of ascorbate on HIF in human cancer cell lines. Ascorbate at physiological concentrations (25 micro M) strikingly suppressed HIF-1alpha protein levels and HIF transcriptional targets, particularly when the system was oncogenically activated in normoxic cells. Similar results were obtained with iron supplementation. These results indicate that both ascorbate and iron availability have major effects on HIF, and imply that the system is commonly regulated by limiting hydroxylase activity under normoxic tissue culture conditions.

Topics: Adenocarcinoma; Ascorbic Acid; Breast Neoplasms; Cell Hypoxia; Endothelial Growth Factors; Female; Ferrous Compounds; Glucose Transporter Type 1; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Intercellular Signaling Peptides and Proteins; Lymphokines; Male; Monosaccharide Transport Proteins; Neoplasms; Ovarian Neoplasms; Procollagen-Proline Dioxygenase; Prostatic Neoplasms; RNA, Messenger; Transcription Factors; Transcriptional Activation; Transferrin; Tumor Cells, Cultured; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors

To examine the prevalence of supplement use in persons before receiving hematopoietic stem cell transplant (HSCT) and the association of select supplements with outcomes.. This observational cohort study included a questionnaire on supplement use before HSCT. Nonrelapse mortality, recurrence/relapse, and mortality or relapse (the inverse of disease-free survival) were followed to two years. Subjects/Setting Persons receiving HSCT at the Fred Hutchinson Cancer Research Center between September 1994 and December 1997 were eligible (N=1,182). Statistical Analyses Performed Descriptive statistics and univariate and Cox regression analyses were conducted.. Sixty-six percent of patients used supplements (31% vitamin C, 19% vitamin E, and 20% herbs or others preparations). Vitamin C at > or =500 mg/day was inversely associated with recurrence among persons with breast cancer (RR=0.11; 95% CI, 0.02-0.89; P=.03). However, among persons with acute leukemia, vitamin C at > or =500 mg/day was positively associated with nonrelapse mortality (RR=2.25; 95% CI, 1.33-3.83; P=.01) and mortality or relapse (RR=1.63; 95% CI, 1.09-2.44; P=.01), respectively. Vitamin E at > or =400 IU/day was positively associated with mortality or relapse (RR=1.77; 95% CI, 1.06 -2.96; P=.02). Applications/Conclusions Though this work was observational, the results suggest supplemental vitamin C before therapy may be beneficial in persons with breast cancer but both vitamin C and vitamin E may increase risk in persons with acute leukemia receiving HSCT. Practitioners should document supplement use in subjects receiving therapy for cancer.

Topics: Adolescent; Adult; Antioxidants; Ascorbic Acid; Breast Neoplasms; Cohort Studies; Dietary Supplements; Disease-Free Survival; Female; Hematopoietic Stem Cell Transplantation; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Acute; Male; Middle Aged; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Proportional Hazards Models; Vitamin E

Intakes of vitamins A, C, and E, folate, and carotenoids have been hypothesized to reduce the risk of breast cancer. However, previous epidemiological studies on these nutrients and breast cancer risk have been inconclusive, and have included primarily postmenopausal women. We examined the intake of these nutrients in relation to breast cancer risk among 90,655 premenopausal women ages 26-46 years in 1991 in the Nurses' Health Study II. Nutrient intake was assessed with a validated food-frequency questionnaire at baseline in 1991 and in 1995. During 8 years of follow-up from 1991 to 1999, we documented 714 incident cases of invasive breast cancer. Overall, none of the vitamins and carotenoids was strongly related to a reduced risk of breast cancer. However, intake of vitamin A, including preformed vitamin A and carotenoids, was associated with a reduced risk of breast cancer among smokers; participants in the highest quintile of total vitamin A intake had a multivariate relative risk of 0.28 (95% confidence interval 0.12-0.62; P, test for trend <0.001; P, test for interaction <0.001) compared with those in the lowest quintile of intake. We found no evidence that higher intakes of vitamins C and E, and folate in early adult life reduce risk of breast cancer. However, intake of vitamin A may be related to a reduced risk of breast cancer among smokers.

Topics: Adult; Ascorbic Acid; Breast Neoplasms; Carotenoids; Diet Surveys; Female; Folic Acid; Humans; Middle Aged; Premenopause; Vitamin A; Vitamin E

To investigate association between breast cancer risk and nutrients intake in Korean women, a case-control study was carried out, at Seoul, Korea. Incident cases (n=224) were identified through the cancer biopsy between February 1999 and December 2000 at two University hospitals in Seoul. Hospital-based controls (n=250) were selected from patients in the same hospitals, during the same periods. Food intake was investigated semiquantitative frequency questionnaire (98 items) by trained dietitian. Subjects were asked to indicate the average food intake and vitamin supplement for a 12 months period of 3-yr prior to the baseline phase. In investigation of vitamin supplement use, subjects were asked the average frequency of use, duration, dose and the brand name of vitamin supplement (multivitamins, vitamin A, vitamin C and vitamin E). And nutrients were calorie adjusted by the residuals method. In this study, higher breast cancer risk incidence was not observed with higher intake of total fat and saturated fatty acids, however statistically significant trends with breast cancer incidence for total saturated fatty acids were found (ptrend=0.0458). In analyses of vitamins, beta-carotene and vitamin C were significantly associated with decreasing risk of breast cancer. In analyses, results from dietary plus supplement of vitamin was not associated with breast cancer risk in this study. In conclusion, our findings suggest that antioxidant vitamins such as beta-carotene and vitamin C intake could lower the breast cancer risk in Korean women.

Topics: Adult; Aged; Antioxidants; Ascorbic Acid; beta Carotene; Breast Neoplasms; Case-Control Studies; Dietary Fats; Dietary Supplements; Female; Humans; Incidence; Korea; Middle Aged; Odds Ratio; Surveys and Questionnaires; Time Factors; Vitamin E; Vitamins

The influence of the vitamins A, C, and E on breast cancer development has not been clarified. An effect of a vitamin per se implicates similar patterns for the effects of the vitamin from dietary and supplemental sources. We examined how the breast cancer incidence rate among postmenopausal women was related to intake of vitamins A, C, and E from diet and supplements.. Data was sampled as case-control nested within the Danish 'Diet, Cancer and Health' cohort. Data on vitamin intakes were collected at entry into the cohort by means of self-administered questionnaires. Women eligible for the nested case-control study were postmenopausal at entry into the cohort. The analyses were based on 418 cases of incident breast cancer and 394 controls (including two cases).. Breast cancer was not significantly related to the intakes of vitamin A or E, whereas a monotonic dose-response relation was seen for the intake of vitamin C. The estimated rate ratio per 100 mg vitamin C was: 2.06 (95% CI: 1.45-2.91) for dietary intake and 1.06 (95% CI: 1.01-1.13) for supplemental intake.. We found no evidence of an association between breast cancer and intake of vitamin A or E for postmenopausal women. For vitamin C we found an increase in breast cancer rate with increasing intake.

Topics: Ascorbic Acid; Breast Neoplasms; Case-Control Studies; Cohort Studies; Denmark; Diet; Dietary Supplements; Female; Humans; Incidence; Middle Aged; Postmenopause; Vitamin A; Vitamin E; Vitamins

In 1998-2000, a case-control study of breast cancer was conducted in Heidelberg, Germany. Three hundred ten consecutively recruited cases with primary breast cancer were matched according to 10-yr age groups to 353 controls with conditions unrelated to diet or endocrine disorders. Intake of raw vegetables, total vegetables, and whole-grain products was inversely associated with breast cancer risk (highest vs. lowest quartile adjusted odds ratio [OR] 0.51, 95% confidence interval [CI] 0.31-0.84; OR = 0.62, 95% CI = 0.38-1.02; and OR = 0.57; 95% CI = 0.34-0.95, respectively). Also, high intake of some selected vitamins and minerals possessing putative DNA-stabilizing properties displayed significant inverse risk associations. Adjusted ORs were as follows: vitamin C (OR = 0.49, 95% CI = 0.2-0.88), folate equivalents (OR = 0.47, 95% CI = 0.25-0.88), b-carotene (OR = 0.46, 95% CI = 0.27-0.80), zinc (OR = 0.35, 95% CI = 0.15-0.78), and copper (OR = 0.51, 95% CI = 0.31-1.03). In contrast, no significant association with risk was seen for an increased intake of fruits, cooked vegetables, fiber, calcium, manganese, or iron. In this population of German women, components of raw vegetables and some micronutrients appear to decrease breast cancer risk.

Topics: Adult; Aged; Ascorbic Acid; beta Carotene; Breast Diseases; Breast Neoplasms; Case-Control Studies; Copper; Diet; Dietary Fiber; DNA; Drug Stability; Edible Grain; Female; Folic Acid; Fruit; Germany; Hot Temperature; Humans; Micronutrients; Middle Aged; Odds Ratio; Risk Factors; Vegetables; Zinc

To correlate the extent of lipid peroxidation with the antioxidant status in the circulation of patients with fibroadenoma and adenocarcinoma of the breast.. Ten fibroadenoma and thirty breast cancer patients and an equal number of age- and sex- matched normal subjects were chosen for the study. Lipid peroxidation as evidenced by thiobarbituric acid reactive substances (TBARS) and the status of the antioxidants superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), glutathione peroxidase (GPx), glutathione S-transferase (GST) ascorbic acid and vitamin E were estimated.. Enhanced lipid peroxidation with concomitant depletion of antioxidants was observed in breast cancer patients as compared to normal subjects and fibroadenoma patients (p < 0.05). A similar pattern of changes was seen in fibroadenoma patients as compared to corresponding normal subjects (p < 0.05).. This study has revealed an imbalance in the redox status in patients with fibroadenoma and adenocarcinoma of the breast.

Topics: Adenocarcinoma; Adolescent; Adult; Antioxidants; Ascorbic Acid; Breast Neoplasms; Catalase; Erythrocytes; Female; Fibroadenoma; Glutathione; Glutathione Peroxidase; Glutathione Transferase; Humans; Lipid Peroxidation; Middle Aged; Oxidation-Reduction; Superoxide Dismutase; Thiobarbituric Acid Reactive Substances; Vitamin E

Topics: Alcohol Drinking; Ascorbic Acid; Breast Neoplasms; Case-Control Studies; Confidence Intervals; Diet; Energy Intake; Female; Humans; Life Style; Middle Aged; Odds Ratio; Portugal; Postmenopause; Risk Factors; Smoking; Surveys and Questionnaires; Vegetables

We tested the effect of different concentrations of ascorbic acid (AA), 50, 100, 250 mg/500 mg/dL) with copper sulfate (CS), 10 mg/dL) on human breast carcinoma (MDA-MB231) cell proliferation in vitro. Cell proliferation was measured using a colori-metric assay (Cell proliferation kit II (XTT), Boehringer, NJ). The results of the mean absorbance of the tissue culture at different AA concentrations and a constant CS concentration were as follow: 0.82 +/- 0.03 (control, mean +/- SE), 0.64 +/- 0.02 (CS above); 0.48 +/- 0.03 (50 mg/dL) AA), 0.21 +/- 0.02 (100 mg/dL), 0.08 +/- 0.01 (250 mg/dL) AA, 0.60 +/- 0.05 (500 mg/dL). These results show that a combination of AA and CS inhibits human breast carcinoma cell proliferation in vitro. This cell proliferation inhibitory effect is directly proportional to the AA concentration with the exception of the 500 mg/dL AA dose. This chemotherapeutic effect was optimally enhanced when AA was added at a concentration of 250 mg/dL. The AA concentrations of 500 mg/dL had a biphasic effect on tumor cell proliferation probably due to back and forth redox reactions between AA and dehydroascorbic acid in a closed system. This study provides preliminary evidence that AA and SC can be used as biological response modifiers (BRM) for tumor growth inhibition.

Topics: Ascorbic Acid; Breast Neoplasms; Cell Division; Copper Sulfate; Drug Screening Assays, Antitumor; Humans; Tumor Cells, Cultured

The MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay is a widely used screening method to measure cell viability and proliferation. When testing the effects of kaempferol on breast cancer cell number (crystal violet staining) and viability (MTT tetrazolium assay) conflicting results were obtained. Cell number decreased but MTT formazan formation increased, suggesting a direct interaction of kaempferol with the MTT tetrazolium reduction. Direct reductive potential was observed in a cell-free system for the presumptive phytoestrogens kaempferol and resveratrol, and extracts of Hypericum perforatum L. and Cimicifuga racemosa L. All agents led to instantaneous dark blue formazan formation in the absence of cells. Additionally, antioxidants such as ascorbic acid, vitamin E and N-acetylcysteine interfered with the MTT tetrazolium assay. When MCF7 and HS578 cells treated with kaempferol were washed before addition of MTT tetrazolium, the direct reduction of dye was reduced significantly. These results indicate that the MTT tetrazolium assay may lead to false positive results when testing natural compounds with intrinsic reductive potential.

Topics: Acetylcysteine; Antioxidants; Ascorbic Acid; Breast Neoplasms; Cell Division; Cell Survival; Drug Interactions; Estrogens, Non-Steroidal; Flavonoids; Humans; Isoflavones; Kaempferols; Phytoestrogens; Plant Extracts; Plant Preparations; Plants; Quercetin; Resveratrol; Stilbenes; Tetrazolium Salts; Thiazoles; Tumor Cells, Cultured; Vitamin E

Improper balance between the production of reactive oxygen metabolites (ROMs), and antioxidative defense system have been defined as oxidative stress in various pathologic conditions. Lipids, lipoproteins and antioxidative vitamins have been associated with the risk of breast cancer. The present case-control study was conducted to investigate the status of antioxidative vitamins (A, C and E), lipids (total cholesterol; TC and triglycerides; TG), lipoproteins (high-density lipoprotein cholesterol; HDL-C and low-density lipoprotein cholesterol; LDL-C) and retinol-binding protein (RBP) in breast cancer patients. The aim of the study was to find out oxidative stress in breast cancer.. Plasma lipids, lipoproteins and vitamins were estimated in 54 untreated breast cancer patients of different clinical stages and in 42 age- and sex-matched controls.. Plasma TC (p < 0.05), and LDL-C and TG (p < 0.01) were found to be significantly elevated among breast cancer patients as compared to the controls. On the other hand, plasma HDL-C concentration (p < 0.001) and vitamin C and E (p < 0.01) were observed significantly decreased in breast cancer patients than in the controls. The maximum changes in plasma TC, and vitamin C and E concentrations were observed in breast cancer patients with stage IV when compared with controls.. The study suggests that higher levels of TC and TG may play important role in carcinogenesis. Furthermore, the elevated plasma LDL-C concentration, which is more susceptible to oxidation, may result in higher lipid peroxidation in breast cancer patients. However, decreased concentrations of HDL-C and vitamin C and E are not likely to be sufficient enough to counter higher ROMs production reported earlier in breast cancer patients that may cause oxidative stress leading to cellular and molecular damage thereby resulting in cell proliferation and malignant conversions.

Topics: Adult; Aged; Ascorbic Acid; Breast Neoplasms; Case-Control Studies; Cholesterol, HDL; Cholesterol, LDL; Female; Humans; Lipids; Lipoproteins; Middle Aged; Oxidative Stress; Retinol-Binding Proteins; Retinol-Binding Proteins, Plasma; Triglycerides; Vitamin A; Vitamin E; Vitamins

Dietary antioxidant vitamins and retinol have been proposed to be protective against breast cancer on the basis of their ability to reduce oxidative DNA damage and their role in cell differentiation. Epidemiologic studies have not been convincing in supporting this hypothesis, but women with high exposure to free radicals and oxidative processes have not been specifically considered. We explored these issues in the Swedish Mammography Screening Cohort, a large population-based prospective cohort study in Sweden that comprised 59,036 women, 40-76 years of age, who were free of cancer at baseline and who had answered a validated 67-item food frequency questionnaire. During 508,267 person-years of follow-up, 1,271 cases of invasive breast cancer were diagnosed. Cox proportional hazards models were used to obtain hazard ratios (HRs) and 95% confidence intervals (CIs). There was no overall association between intake of ascorbic acid, beta-carotene, retinol or vitamin E and breast cancer incidence. High intake of ascorbic acid was inversely related to breast cancer incidence among overweight women (HR=0.61; 95% CI 0.45-0.82, for highest quintile of intake among women with body mass index>25 kg/m(2)) and women with high consumption of linoleic acid (HR=0.72; 95% CI 0.52-1.02, for highest quintile of ascorbic acid intake and average consumption of more than 6 grams of linoleic acid per day). Among women with a body mass index of 25 or below, the hazard ratio for breast cancer incidence was 1.27 (95% CI 0.99-1.63), comparing the highest to the lowest quintile of ascorbic acid intake. Consumption of foods high in ascorbic acid may convey protection from breast cancer among women who are overweight and/or have a high intake of linoleic acid.

Topics: Adult; Aged; Antioxidants; Ascorbic Acid; beta Carotene; Body Weight; Breast Neoplasms; Cell Differentiation; Cohort Studies; Diet; DNA Damage; Female; Follow-Up Studies; Humans; Linoleic Acid; Mammography; Middle Aged; Oxygen; Proportional Hazards Models; Surveys and Questionnaires; Sweden; Vitamin A; Vitamin E

Laboratory data suggest that several different vitamins may inhibit the growth of mammary cancers, however epidemiologic data on the relationship between vitamin supplement use and breast cancer are inconsistent. We examined the association between self-reported vitamin supplement use and breast cancer among black women and white women.. The data came from a population-based, case-control study conducted in North Carolina between 1993 and 1996. Logistic regression models were used to calculate adjusted odds ratios (ORs) for breast cancer associated with the use of multivitamins or individual vitamin supplements.. Eligible cases were aged 20 to 74, and approximately 40% of the study population were black women. The analyses included 861 cases and 790 controls.. Among all women, there was little evidence for an association between any vitamin supplement and breast cancer. Modest inverse associations were observed among white women for use of multivitamins 95% confidence interval (CI): 0.59-1.12), vitamin C 95% CI: 0.54-1.14) and vitamin E 95% CI: 0.49-1.13). There was no evidence that vitamin supplements reduced the risk of breast cancer among black women.. This study provided very limited support for the hypothesis that vitamin supplements may reduce the risk of breast cancer. Although dietary factors are likely an important influence in breast cancer aetiology, reductions in risk are most likely to be achieved through dietary modification rather than through vitamin supplementation.

Topics: Adult; Aged; Ascorbic Acid; Black or African American; Breast Neoplasms; Case-Control Studies; Dietary Supplements; Female; Humans; Middle Aged; North Carolina; Odds Ratio; Risk Factors; Vitamin E; Vitamins; White People

Combined application of cyclophosphamide, methotrexate, 5-fluorouracil (CMF) has been followed in the treatment of breast cancer. The combined effect of CMF and vitamin C on plasma lipid and lipoprotein is important, since vitamin C encumbers the lipid abnormalities instigated by CMF. Hence, the study was launched to appraise the salubrious role of vitamin C in CMF administered fibrosarcoma-bearing rats. Fibrosarcoma cell line-induced rats were treated with CMF (cyclophosphamide 10 mg/kg b.w., methotrexate 1 mg/kg b.w., 5-fluorouracil 10 mg/kg b.w. and vitamin C 200 mg/kg b.w.) individually and in combination for 120 days. The concentration of plasma lipids and lipoprotein was determined in control and experimental rats. The untreated as well as CMF administered fibrosarcoma-bearing rats divulged significantly in increased levels of plasma total cholesterol, triglycerides, phospholipids, very low density lipoprotein (VLDL) and low density lipoprotein (LDL) cholesterol, as compared with their respective control animals. Whereas ester and high density lipoprotein (HDL) cholesterol levels exhibited a marked decrease in these animals. However, these lipid abnormalities were found to be moderated by co-administration of vitamin C. These results suggested that some clinical entanglement of CMF was refrained by co-administration of vitamin C in tumor stress condition.

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Ascorbic Acid; Breast Neoplasms; Cholesterol; Cyclophosphamide; Female; Fibrosarcoma; Fluorouracil; Lipid Metabolism; Lipids; Methotrexate; Neoplasm Transplantation; Neoplasms, Experimental; Rats; Rats, Wistar

Low levels of selenium have been associated with a higher risk of cardiovascular diseases and cancer in humans. Since 1984, selenium supplementation through fertilizers has been employed in Finland to increase the very low concentration of selenium in the nation's food supply. As a result, the selenium concentration of Finnish foods became one of the highest in Europe. A decade after selenium supplementation began, the association between toenail selenium and the risk of breast cancer was examined.. Case-control study.. Eastern Finland.. 289 pre- and postmenopausal breast cancer cases and 433 community controls. The diagnosis was unknown at the time the toenail samples were collected.. The mean toenail selenium concentration was 0.80 mg/kg in premenopausal cases and 0.84 mg/kg in premenopausal controls: and 0. 77 mg/kg in postmenopausal cases and 0.80 mg/kg in postmenopausal controls. The odds ratio (OR) comparing the highest with the lowest quintiles of toenail selenium concentration was 1.1 (95% CI 0.4-3.2) in premenopausal women and 0.7 (95% CI 0.3-1.5) in postmenopausal women. The intake of retinol, beta-carotene, vitamin E and vitamin C did not change the association between toenail selenium and breast cancer.. A decade after selenium supplementation, selenium seems not to be an important factor in the etiology of breast cancer, neither in premenopausal nor postmenopausal women.. This work was supported by the EVO funds from the Kuopio University Hospital and by research grants from the Academy of Finland, Yrjö Jahnsson Foundation and Juho Vainio Foundation. European Journal of Clinical Nutrition (2000) 54, 98-103

Topics: Adult; Aged; Aging; Ascorbic Acid; beta Carotene; Breast Neoplasms; Case-Control Studies; Female; Finland; Humans; Middle Aged; Nails; Odds Ratio; Postmenopause; Premenopause; Risk Factors; Selenium; Vitamin A; Vitamin E

To investigate the association between prediagnostic plasma ascorbic acid concentrations and subsequent breast cancer risk in a nested case-control study.. Female volunteer residents of Washington County, MD, donated 14,625 non-fasting blood samples in 1989. Incident breast cancer cases (n = 115) and controls (n = 115) were matched by age, menopausal status at donation, and date and hour of blood donation.. Median ascorbic acid concentrations were similar between cases and controls (1.44 mg/dl vs. 1.39 mg/dl. p = 0.78). There was no evidence for a dose-response relationship between higher plasma ascorbic acid concentrations and breast cancer risk [highest vs. lowest fifths: ORadjusted = 0.90, Ptrend = 0.98).. Findings from this prospective study do not suggest a protective association between prediagnostic plasma ascorbic acid concentrations and breast cancer risk in the subsequent 5 years of follow-up.

Topics: Ascorbic Acid; Breast Neoplasms; Case-Control Studies; Female; Humans; Incidence; Maryland; Menopause; Prospective Studies; Risk Factors; Surveys and Questionnaires

To determine whether self-reported frequencies of food use were linked to self-reported preferences for the same foods. The hypothesis was that both food frequencies and food preferences can predict nutrient intakes.. Participants were adult women patients (n = 339), recruited through the University of Michigan Breast Care Center. The sample included both persons with breast cancer and persons who were cancer-free.. All women completed a 98-item food frequency questionnaire and rated preferences for many of the same foods using a 9-point category scale. Percent energy from fat and saturated fat, and intakes of dietary fiber and vitamin C were estimated from analyses of 4-day food records.. Pearson correlations coefficients were used for data analysis.. Dislike was a strong predictor of nonuse. In contrast, the more preferred foods were also reported as more frequently consumed. Significant correlations between preference and frequency scores were obtained for virtually all item pairs. Median Pearson correlation coefficient was 0.30 (range 0.04 to 0.56). Correlations improved when foods were aggregated into the chief dietary sources of fat, saturated fat, and vitamin C. Food frequencies and food preferences showed the same strength of association with percent energy from fat and saturated fat (r = 0.20 to 0.25). Food frequencies showed a stronger association with vitamin C intakes than did preferences for vegetables and fruit.. Food preferences may provide a potential alternative to the food frequency approach.

Topics: Adult; Aged; Aged, 80 and over; Ascorbic Acid; Breast Neoplasms; Diet; Diet Records; Dietary Fats; Dietary Fiber; Eating; Feeding Behavior; Female; Food Preferences; Humans; Middle Aged; Statistics as Topic; Surveys and Questionnaires

Glutathione-S-transferases catalyze the detoxication of carcinogen metabolites and reactive oxygen species (ROS) produced through a number of mechanisms. Glutathione-S-transferase (GST) M1 is polymorphic, and the null allele results in a lack of enzyme activity. Because there are indications that ROS may be involved in breast carcinogenesis, we sought to determine whether the GSTM1 null allele was associated with increased breast cancer, particularly among women with lower consumption of dietary sources of alpha-tocopherol, carotenoids and ascorbic acid. In a study of diet and cancer in western New York, women with primary, incident, histologically confirmed breast cancer (n = 740) and community controls (n = 810) were interviewed and an extensive food-frequency questionnaire administered. A subset of these women provided a blood specimen. DNA was extracted and genotyping performed for GSTM1. Data were available for 279 cases and 340 controls. The null allele did not increase breast cancer risk, regardless of menopausal status. There were also no differences in associations between the polymorphism and risk among lower and higher consumers of dietary sources of antioxidants or smokers and nonsmokers. These results indicate that GSTM1 genetic polymorphisms are not associated with breast cancer risk, even in an environment low in antioxidant defenses.

Topics: Antioxidants; Ascorbic Acid; Breast Neoplasms; Carotenoids; Diet; Female; Fruit; Glutathione Transferase; Humans; Polymorphism, Genetic; Postmenopause; Premenopause; Reactive Oxygen Species; Risk Factors; Vegetables; Vitamin E

Data on intake of specific carotenoids and breast cancer risk are limited. Furthermore, studies of vitamins A, C, and E in relation to breast cancer risk are inconclusive. We have conducted a large, prospective study to evaluate long-term intakes of these nutrients and breast cancer risk.. We examined, by use of multivariate analysis, associations between intakes of specific carotenoids, vitamins A, C, and E , consumption of fruits and vegetables, and breast cancer risk in a cohort of 83234 women (aged 33-60 years in 1980) who were participating in the Nurses' Health Study. Through 1994, we identified 2697 incident cases of invasive breast cancer (784 premenopausal and 1913 postmenopausal).. Intakes of beta-carotene from food and supplements, lutein/zeaxanthin, and vitamin A from foods were weakly inversely associated with breast cancer risk in premenopausal women. Strong inverse associations were found for increasing quintiles of alpha-carotene, beta-carotene, lutein/zeaxanthin, total vitamin C from foods, and total vitamin A among premenopausal women with a positive family history of breast cancer. An inverse association was also found for increasing quintiles of beta-carotene among premenopausal women who consumed 15 g or more of alcohol per day. Premenopausal women who consumed five or more servings per day of fruits and vegetables had modestly lower risk of breast cancer than those who had less than two servings per day (relative risk [RR] = 0.77; 95% confidence interval [CI] = 0.58-1.02); this association was stronger among premenopausal women who had a positive family history of breast cancer (RR = 0.29; 95% CI = 0.13-0.62) or those who consumed 15 g or more of alcohol per day (RR = 0.53; 95% CI = 0.27-1.04).. Consumption of fruits and vegetables high in specific carotenoids and vitamins may reduce premenopausal breast cancer risk.

Topics: Adult; Ascorbic Acid; beta Carotene; Breast Neoplasms; Carotenoids; Diet; Feeding Behavior; Female; Humans; Middle Aged; Multivariate Analysis; Premenopause; Prospective Studies; Risk; Surveys and Questionnaires; Vitamin A; Vitamin E

Although several dietary compounds are hypothesized to have anticarcinogenic properties, the role of specific micronutrients in the development of breast cancer remains unclear. To address this issue, we assessed intake of retinol, beta-carotene, vitamin C and vitamin E in relation to breast cancer risk in a case-control study in Greece. Eight hundred and twenty women with histologically confirmed breast cancer were compared with 1548 control women. Dietary data were collected through a 115-item semiquantitative food frequency questionnaire. Data were modelled by logistic regression, with adjustment for total energy intake and established breast cancer risk factors, as well as mutual adjustment among the micronutrients. Among post-menopausal women, there was no association between any of the micronutrients evaluated and risk of breast cancer. Among premenopausal women, beta-carotene, vitamin C and vitamin E were each inversely associated with breast cancer risk, but after mutual adjustment among the three nutrients only beta-carotene remained significant; the odds ratio (OR) for a one-quintile increase in beta-carotene intake was 0.84 (95% confidence interval 0.73-0.97). The inverse association observed with beta-carotene intake, however, is slightly weaker than the association previously observed with vegetable intake in these data, raising the possibility that the observed beta-carotene effect is accounted for by another component of vegetables.

Topics: Ascorbic Acid; Breast Neoplasms; Case-Control Studies; Diet Records; Female; Greece; Humans; Likelihood Functions; Postmenopause; Premenopause; Risk Factors; Surveys and Questionnaires; Vitamin A; Vitamin E

Human tumors may contain high concentrations of ascorbic acid, but little is known about how they acquire the vitamin. Certain specialized cells can transport ascorbic acid directly through a sodium ascorbate cotransporter, but in most cells, vitamin C enters through the facilitative glucose transporters (GLUTs) in the form of dehydroascorbic acid, which is then reduced intracellularly and retained as ascorbic acid. Mice with established hematopoietic and epithelial cell xenografts were studied for the accumulation of injected ascorbic acid and dehydroascorbic acid. Most hematopoietic and epithelial tumor cell lines can only transport vitamin C in the oxidized form (dehydroascorbic acid) in vitro; however, when grown as xenografts in mice, they rapidly accumulated vitamin C after administration of radiolabeled ascorbic acid. The involvement of the GLUTs in vitamin C uptake by the xenografted tumors was demonstrated by competitive inhibition with D-glucose but not L-glucose. Because the malignant cells were not capable of directly transporting ascorbic acid, we reasoned that the ascorbic acid was oxidized to dehydroascorbic acid in the tumor microenvironment. Tumor accumulation of vitamin C in animals injected with ascorbic acid was inhibited by coadministration of superoxide dismutase, implying a role for superoxide anion in the oxidation of ascorbic acid. Whereas the epithelial cancer cell lines could not generate superoxide anion in culture, the minced xenograft tumors did. Our studies show the transport of dehydroascorbic acid by GLUTs is a means by which tumors acquire vitamin C and indicate the oxidation of ascorbic acid by superoxide anion produced by cells in the tumor stroma as a mechanism for generating the transportable form of the vitamin.

Topics: Animals; Ascorbic Acid; Biological Transport; Breast Neoplasms; Female; Glucose; Glucose Transporter Type 1; HL-60 Cells; Humans; Male; Mice; Mice, Nude; Models, Biological; Monosaccharide Transport Proteins; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prostatic Neoplasms; Stromal Cells; Transplantation, Heterologous

To evaluate whether the protective effect associated with vegetables and fruits in breast cancer could be explained by nutrients and bioactive substances present in these plant foods, we carried out a case-control study in Uruguay including 400 cases and 405 controls. The intake of vegetables, fruits, and related nutrients was estimated with a food frequency questionnaire on 64 food items. This questionnaire allowed the calculation of total energy intake, and nutrients were calorie adjusted by the residuals method. Odds ratios for study variables were estimated by unconditional multiple logistic regression. Total vegetable, total fruit, dietary fiber, vitamin C, vitamin E, lycopene, folate, and total phytosterol intakes were inversely associated with breast cancer risk [4th quartile odds ratio for total vegetable intake = 0.41, 95% confidence interval = 0.26-0.65, p (for trend) = 0.004]. The association with total vegetable intake was not independent of lycopene intake. The results related to vegetable and nutrient intakes are consistent with antioxidant and antiestrogenic effects. This could be mediated, among other nutrients, by dietary fiber and lycopene intake. The role of other unmeasured phytochemicals, correlated with dietary fiber and lycopene intakes, cannot be ruled out.

Topics: Ascorbic Acid; Breast Neoplasms; Carotenoids; Case-Control Studies; Diet Records; Dietary Fiber; Energy Intake; Female; Folic Acid; Fruit; Humans; Lycopene; Phytosterols; Risk Factors; Surveys and Questionnaires; Uruguay; Vegetables; Vitamin E

Topics: Adult; Age Factors; Aged; Ascorbic Acid; Breast Neoplasms; Chromatography, High Pressure Liquid; Female; Humans; Middle Aged; Postmenopause; Premenopause; Vitamin A; Vitamin E

Association between breast cancer risk and the intake of vitamins C and E, retinol, beta (beta)-carotene, dietary fibre, vegetables, fruit and potatoes was examined in The Netherlands Cohort Study, for 62,573 women aged 55-69 years. After 4.3 years of follow-up, 650 incident breast cancer cases were identified. After adjusting for traditional risk factors, breast cancer risk was not influenced by the intake of beta-carotene, vitamin E, dietary fibre, supplements with vitamin C, vegetables or potatoes. Fruit consumption showed a non-significant inverse association with breast cancer risk (RR highest/lowest quintile = 0.76, 95% CI 0.54-1.08). A small reduction in risk was also observed with increasing intake of dietary vitamin C (RR highest/lowest quintile = 0.77, 95% CI 0.55-1.08). For retinol, a weak positive association was observed (RR highest/lowest quintile = 1.24, 95% CI 0.83-1.83). Among subjects with a high intake of polyunsaturated fatty acids (PUFAs), both beta-carotene and vitamin C intake showed a non-significant inverse association with breast cancer risk (P-trend = 0.15 and 0.16 respectively). Our findings do not suggest a strong role, if any, for intake of vitamins C and E, beta-carotene, retinol, dietary fibre, vegetables, fruit and potatoes in the aetiology of breast cancer.

Topics: Aged; Ascorbic Acid; beta Carotene; Breast Neoplasms; Cohort Studies; Diet Surveys; Dietary Fiber; Female; Fruit; Humans; Middle Aged; Odds Ratio; Prospective Studies; Risk; Surveys and Questionnaires; Vegetables; Vitamin A; Vitamin E

Although many epidemiological studies indicate protective effect of vitamin C against a variety of human malignancies its mechanism(s) of action is questionable. The presented results show that the part of its effect may be accomplished by mononuclear cells, as necessary participants in body defence. Namely, in a long-term in vitro assay we tested vitamin C influence on random migration ability of malignant pleural effusion mononuclears (PEM) obtained from breast cancer patients. Vitamin C in a dose- (50-500 micrograms) and time-dependent (4-44 h) manner inhibited PEM motility, suggesting that immobilization of cells in situ may contribute to its beneficial effect in human cancers.

Topics: Ascorbic Acid; Breast Neoplasms; Carcinoma; Cell Migration Inhibition; Cell Movement; Female; Humans; Leukocytes, Mononuclear; Pleural Effusion, Malignant; Pleural Neoplasms

Given the international variations in breast cancer incidence rates and the changes in breast cancer incidence among migrant populations, it has been hypothesized that diet is a factor influencing risk of this disease. Many studies indicate that a diet high in vegetables and fruits may protect against breast cancer.. We conducted a case-control study of diet, including the intake of non-food supplements, and premenopausal breast cancer risk. We evaluated in detail usual intake of vegetables and fruits (each measured as the total reported grams consumed for all queried vegetables and fruit), vitamins C and E, folic acid, individual carotenoids, and dietary fiber with its components.. Case patients (n=297) were identified through pathology records from hospitals in Erie and Niagara counties in western New York. They consisted of premenopausal women 40 years of age or oder who were diagnosed with breast cancer from November 1986 through April 1991. Control subjects (n=311), frequency-matched to case patients on the basis of age and county of residence, were randomly selected from New York State Department of Motor Vehicles records. In-person interviews included detailed reports of usual diet in the period 2 years before the interview. Unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs).. There was a reduction in risk associated with high intake of several nutrients. With the lowest quartile of intake as the referent, adjusted ORs for the highest quartile of intake for specific nutrients were as follows: vitamin C (OR=0.53; 95% CI=0.33-0.86), alpha-tocopheral (OR=0.55; 95% CI=0.34-0.88), folic acid (OR=0.50; 95% CI=0.31-0.82), alpha-carotene (OR=0.67; 95% CI=0.42-1.08) and beta-carotene (OR=0.46; 95% CI=0.28-0.74), lutein + zeaxanthin (OR=0.47; 95% CI=0.28.0-77), and dietary fiber from vegetables and fruits (OR=0.48; 95% CI=0.30-0.78). No association with risk was found for beta-cryptoxanthin, lycopene, or grain fiber. Fruits were weakly associated with a reduction in risk (fourth quartile OR=0.67; 95% CI=0.42-1.09). No association was found between breast cancer risk and intake of vitamins C and E and folic acid taken as supplements. A strong inverse association between total vegetable intake and risk was observed (fourth quartile OR=0.46; 95% CI=0.28-0.74). This inverse association was found to be independent of vitamin C,alpha-tocopherol, folic acid, dietary fiber, and alpha-carotene. Adjusting for beta-carotene or lutein + zeaxanthin somewhat attenuated the inverse association with vegetable intake.. In this population, intake of vegetables appears to decrease premenopausal breast cancer risk. This effect may be related, in part, to beta-carotene and lutein + zeaxanthin in vegetables. It appears, however, that, of the nutrients and food components examined, no single dietary factor explains the effect. Evaluated components found together in vegetables may have a synergistic effect on breast cancer risk; alternatively, other unmeasured factors in these foods may also influence risk.

Topics: Adult; Ascorbic Acid; Breast Neoplasms; Carotenoids; Case-Control Studies; Diet; Dietary Fiber; Evaluation Studies as Topic; Folic Acid; Fruit; Humans; Male; Middle Aged; Premenopause; Risk Factors; Vegetables; Vitamin E

Utilizing a microplate ATP bioluminescence assay, two human breast carcinoma cell lines, MCF-7 and MDA-MB-231, were tested against doxorubicin (DOX), cisplatin (DDP), and paclitaxel (Tx) alone and in combination with ascorbic acid (Vit C). In both cell lines, Vit C exhibited cytotoxic activity at high concentrations (i.e. 10(2)-10(3) microM). Both cell lines also were resistant to DOX. MCF-7 was found to be DDP-resistant, MDA-MB-231 was moderately sensitive to DDP. Both cell lines were strongly sensitive to Tx. Vit C both at non-cytotoxic (1 microM) and moderately cytotoxic concentrations (10(2) microM) improved the cytotoxicity of DOX, DDP, and Tx significantly. Combination effects between Vit C and DDP or Tx were partly synergistic and partly additive or subadditive whereas a consistent synergism was found between Vit C and DOX. The mechanisms by which Vit C potentiates the cytostatics studied are yet unclear and should be evaluated further.

Topics: Antineoplastic Agents; Ascorbic Acid; Breast Neoplasms; Cell Survival; Cisplatin; Doxorubicin; Drug Synergism; Female; Humans; Paclitaxel; Receptors, Estrogen; Tumor Cells, Cultured

The association between dietary antioxidant vitamin intake and the risk of breast cancer was examined in a prospective study of 34,387 postmenopausal women in Iowa. Intakes of vitamins A, C, and E and of retinol and carotenoids were assessed in 1986 by mailed semiquantitative food frequency questionnaire. Through December 31, 1992, 879 incident breast cancer cases occurred in this cohort. There was little suggestion that breast cancer risk was associated with differences in intake of these vitamins. For example, from the lowest to highest total vitamin A intake categorized by quintiles, the age-adjusted relative risks of breast cancer were 1.0, 0.95, 1.17, 1.20, and 0.90 (p trend = 0.92). Similarly unremarkable relative risk patterns were seen for the intakes of vitamins C and E and of retinol and carotenoids. These findings were not altered after adjustment for breast cancer risk factors or in analyses confined to women who reported no supplemental vitamin intake. Exclusion of cases that occurred in the first 2 years of follow-up, under the assumption that women may have increased intake of these vitamins in response to preclinical symptoms of breast cancer, did not suggest an inverse association of these vitamins with the risk of breast cancer. Women who reported consuming at least 500 mg/day of supplemental vitamin C had a relative risk of breast cancer of 0.79 compared with women who did not take supplemental vitamin C, and women who reported consuming more than 10,000 IU/day of vitamin A had a corresponding relative risk of 0.73. However, these relative risks were not statistically significant. These results provide little evidence that intake of these vitamins is associated with breast cancer risk.

Topics: Aged; Ascorbic Acid; Breast Neoplasms; Diet; Female; Humans; Incidence; Iowa; Middle Aged; Nutrition Surveys; Postmenopause; Prospective Studies; Risk; Risk Factors; Vitamin A; Vitamin E

Levels of carotene, vitamin A, and vitamin C measured in the serum of patients with cancer of the breast and uterine cervix were compared with levels in healthy controls and patients with benign diseases of the breast and cervix. Serum ascorbate levels were significantly lower in patients with benign diseases of the breast and cervix than in controls. In cancer patients, there was a significant trend of lower serum vitamin levels with increasing stage of the disease.

Topics: Ascorbic Acid; Breast Neoplasms; Carotenoids; Female; Humans; Reference Values; Uterine Cervical Neoplasms; Vitamin A

The ability of human cells to regenerate ascorbic acid from dehydroascorbate is partially dependent on the glutathione redox status of the cell and the relative activity of dehydroascorbate reductases. Mammalian dehydroascorbate reductase activity is associated with two proteins known as thioltransferase (glutaredoxin) and protein disulfide isomerase. We compared the specific activity of thioltransferase, protein disulfide isomerase, and other GSH-related enzymes in Adriamycin-resistant human breast tumor cells, MCF-7 ADRR, and Adriamycin-sensitive, MCF-7 WT, tumor cells. MCF-7 ADRR cells had higher activities of glutathione peroxidase (34.7 fold), nonseleno-glutathione peroxidase (glutathione S-transferases; 5.3 fold), thioredoxin (2.3 fold), and thioltransferase (4.0 fold) compared with the WT Adriamycin-sensitive cell line. Thioltransferase was detected in Western blots in extracts of ADRR MCF-7 cells but not in WT MCF-7 cells. alpha-Tocopherol in the membrane and cytosolic fractions was 2.8 and 3.0 fold higher, respectively, in Adriamycin-resistant compared with Adriamycin-sensitive cells. Supplementation of MCF-7 cells with L-ascorbic acid 2-phosphate (2 and 10 mM) had no effect on WT cell viability after 5 days incubation with up to 0.33 microM Adriamycin. In contrast, supplementation of ADRR MCF-7 cells with L-ascorbic acid 2-phosphate resulted in enhanced resistance up to 3.4 microM Adriamycin over a 5-day incubation. Both lines of MCF-7 cells demonstrated the ability to utilize ascorbic acid as the 2-phosphate derivative. After 48 h incubation with 8.6 microM Adriamycin, the resistant cells maintained normal viability and ascorbate-dehydroascorbate levels, whereas drug-sensitive cells had significantly lower ascorbate with a higher percent dehydroascorbate and increased cell death as judged by cell protein levels (52% of controls).

Topics: Animals; Ascorbic Acid; Blotting, Western; Breast Neoplasms; Cell Survival; Cells, Cultured; Dose-Response Relationship, Drug; Doxorubicin; Glutaredoxins; Humans; Oxidoreductases; Proteins; Rats

We sought to determine if specific dietary antioxidants may be particularly effective in reducing breast cancer risk for women reporting family history (FH) of breast cancer in a first-degree relative. Interviews regarding usual diet, health, and family histories were conducted with 262 premenopausal and 371 postmenopausal women with incident, primary breast cancer from western New York (United States). These women were frequency-matched by age and county of residence with community controls. Among premenopausal women, there was a significant interaction between FH and alpha-tocopherol; alpha-tocopherol was associated with significantly decreased risk among FH+ women (adjusted fourth-quartile odds ratio [OR] = 0.01, 95 percent confidence interval [CI] = 0.0-0.3). This association was much weaker for FH- women [OR = 0.7, CI = 0.4-1.2]. For FH- women, a significant inverse association was observed between beta-carotene and premenopausal breast-cancer risk (OR = 0.4, CI = 0.3-0.5), but not for FH+ women (OR = 0.5, CI = 0.1-4.0). Similar relationships, although not as strong, were noted among postmenopausal women. Although limited by small numbers, these results suggest that biologic mechanisms of tumorigenesis may differ in FH+ and FH- women, and that alpha-tocopherol may be a potential chemopreventive agent for women with a family history of breast cancer, particularly premenopausal women.

Topics: Adult; Aged; Aged, 80 and over; Antioxidants; Ascorbic Acid; beta Carotene; Breast Neoplasms; Carotenoids; Case-Control Studies; Confidence Intervals; Diet; Female; Humans; Incidence; Logistic Models; Middle Aged; New York; Postmenopause; Premenopause; Risk Factors; Vitamin E

Topics: Antioxidants; Ascorbic Acid; beta Carotene; Breast Neoplasms; Carotenoids; Case-Control Studies; Diet; Family; Female; Humans; Odds Ratio; Risk Factors; Vitamin E; Vitamins

A case-control study of the role of diet in the cause of breast cancer was conducted between 1988 and 1991 in Navarra, North Spain; 100 women with breast cancer and 100 hospital controls admitted during the same period were interviewed, using a food frequency-consumption questionnaire. Cases reported significantly lower consumption of fruits, vegetables and fish; relative risk (RR) for persons in the lowest tertile of consumers was: fruits, RR = 3.83, confidence limit (CL) = 9.12-1.66, P = 0.01; vegetables, RR = 1.92, CL = 4.57-0.80, P = 0.09; fish, RR = 0.32, CL = 6.31-0.83, P = 0.05. The risk increased for persons in the highest tertile of processed meat intake, RR = 3.20, P = 0.05. Nutrient intakes for individuals were estimated by multiplying the nutrient content of a selected typical portion size for each specified food item by the frequency that the food was used per month, and adding these estimates for all food items. Cases reported significantly less frequent consumption of vitamin C (ascorbic acid) and monounsaturated fatty acid; after controlling for total calorie intake, the RR was estimated for consumption of vitamin C (RR = 0.40, CL = 0.2-0.9), and monounsaturated fatty acid (RR = 0.30, CL = 0.1-1.08).

Topics: Adult; Alcohol Drinking; Animals; Ascorbic Acid; Breast Neoplasms; Case-Control Studies; Diet; Dietary Carbohydrates; Dietary Proteins; Energy Intake; Fatty Acids, Monounsaturated; Female; Fishes; Fruit; Humans; Meat; Menopause; Middle Aged; Risk Factors; Spain; Urban Health; Vegetables

Electron spin resonance (ESR) spectroscopy and oxygen consumption measurements using a Clark-type oxygen electrode have been used to study the metabolism of the estrogen 17 beta-estradiol by lactoperoxidase. Evidence for a one-electron oxidation of estradiol to its reactive phenoxyl radical intermediate is presented. The phenoxyl radical metabolite abstracts hydrogen from reduced glutathione generating the glutathione thiyl radical, which is spin trapped by 5,5-dimethyl-1-pyrroline N-oxide (DMPO) and subsequently detected by ESR spectroscopy. In the absence of DMPO, molecular oxygen is consumed by a sequence of reactions initiated by the glutathione thiyl radical. Similarly, the estradiol phenoxyl radical abstracts hydrogen from reduced beta-nicotinamide-adenine dinucleotide (NADH) to generate the NAD. radical. The NAD. radical is not spin trapped by DMPO, but instead reduces molecular oxygen to the superoxide radical, which is then spin-trapped by DMPO. The superoxide generated may either spontaneously dismutate to form hydrogen peroxide or react with another NADH to form NAD., thus propagating a chain reaction leading to oxygen consumption and hydrogen peroxide accumulation. Ascorbate inhibits oxygen consumption when estradiol is metabolized in the presence of either glutathione or NADH by reducing radical intermediates back to their parent molecules and forming the relatively stable ascorbate radical. These results demonstrate that the futile metabolism of micromolar quantities of estradiol catalyzes the oxidation of much greater concentrations of biochemical reducing cofactors, such as glutathione and NADH, with hydrogen peroxide produced as a consequence. The accumulation of intracellular hydrogen peroxide could explain the hydroxyl radical-induced DNA base lesions recently reported for female breast cancer tissue.

Topics: Ascorbic Acid; Breast Neoplasms; Estradiol; Female; Free Radicals; Glutathione; Humans; Hydrogen Peroxide; Lactoperoxidase; NAD; Oxidative Stress; Superoxide Dismutase

This county-based correlation study examined associations of breast cancer mortality with dietary habits and certain serum biochemical markers, utilizing data collected from an ecological survey in 65 Chinese rural counties. Univariate correlation and multivariate regression analysis showed that consumption of animal foods, including eggs, fish and meat, was positively linked to county-wide mortality rates of breast cancer in Chinese women. No clear associations between breast cancer mortality rates and consumption of green vegetables, carrots and fruits were observed in this study. A modest inverse correlation between serum vitamin C levels and breast cancer mortality was observed, while selenium levels were positively related to the mortality rates. Positive correlations for serum ferritin and hemoglobin were found, in agreement with recent reports of an elevated cancer risk with increased body iron stores. Limitations of these ecological data preclude causal inferences, but the findings provide clues to breast cancer risk and protective factors in a low incidence area of the world.

Topics: Adult; Analysis of Variance; Ascorbic Acid; Biomarkers, Tumor; Breast Neoplasms; China; Diet; Female; Hemoglobins; Humans; Life Style; Menarche; Middle Aged; Multivariate Analysis; Socioeconomic Factors

Consumption of a high-fat diet has been associated with poor survival in breast cancer patients. However, studies examining this association are limited and have not used adjustment of energy in their estimates.. The effect of usual diet before diagnosis of breast cancer on the risk of dying of breast cancer was examined in a cohort of women with breast cancer from the National Breast Screening Study (NBSS) in Canada.. From a cohort of 89,835 women in the NBSS, a total of 1270 histologically confirmed cases of invasive carcinoma of the breast were identified by active follow-up, supplemented by passive follow-up involving record linkage to provincial cancer registries. Of these, 678 case patients who had completed a diet history and were diagnosed from January 1982 up to June 1992 formed the cohort for this investigation. Diet was ascertained from a self-administered diet-history questionnaire. Mortality data were obtained by linkage to the Canadian Mortality Data Base of Statistics Canada, provincial cancer registries, and annual follow-up of cases through physicians. Risk of dying and survival probabilities were estimated by the Cox proportional hazards method and the actuarial life-table method.. There were 83 deaths in this study cohort of 678 women; 76 deaths were due to breast cancer, and the remaining seven resulted from other causes. The 5-year survival rate was 90%. For every 5% increase in energy from saturated fat, the risk of dying of breast cancer increased by 50% (hazard ratio = 1.50; 95% confidence interval [CI]: 1.08-2.08). No significant increase in risk was seen with total fat intake (hazard ratio = 1.21; 95% CI = 0.91-1.61) or oleic acid intake (hazard ratio = 1.25; 95% CI = 0.90-1.74). There was a lower risk of dying of breast cancer in the highest quartiles of beta carotene intake (hazard ratio = 0.48; 95% CI = 0.23-0.99) and vitamin C intake (hazard ratio = 0.43; 95% CI: 0.21-0.86); both vitamins showed a significant dose-response relationship (P for trend, < or = .05). These effects varied with menopausal status at diagnosis and tumor characteristics.. These results suggest an increased risk of dying of breast cancer with higher intakes of saturated fat before diagnosis and slightly reduced risk with higher intakes of beta carotene and vitamin C.. More attention should be paid to premorbid dietary habits in relation to breast cancer prognosis. Further studies, however, need to be done with full ascertainment of dietary changes prior to and subsequent to diagnosis.

Topics: Adult; Ascorbic Acid; beta Carotene; Breast Neoplasms; Carotenoids; Diet; Dose-Response Relationship, Drug; Female; Humans; Life Tables; Middle Aged; Prognosis; Proportional Hazards Models

Our findings from a previous study, that increased consumption of beta-carotene and vitamin C is associated with favourable prognostic indices in patients with breast cancer, have been borne out by our current study of patient survival over a 6-year period. The results of the current study point to beta-carotene consumption as the dietary variable most significantly associated with improved survival. Only one death occurred in the group with the highest consumption of beta-carotene, while there were eight and 12 deaths in the intermediate and lowest groups of consumption respectively. The possible antiproliferative effects of beta-carotene have been recognised for some time, with investigations being focused more recently on its derivative, retinoic acid, which has been found to improve differentiation in many tissues, including cell lines derived from mammary carcinomas. Retinoids have been associated with significant clinical responses in a variety of tumours, and chemoprevention trials using beta-carotene have been undertaken for many malignancies. However, beta-carotene has not yet been used in clinical trials to evaluate its potential for the treatment of breast cancer. A large-scale clinical trial is necessary to determine the effectiveness of beta-carotene in reducing the chances of recurrence of breast cancer, and in preventing the development of new cancers.

Topics: Ascorbic Acid; beta Carotene; Breast Neoplasms; Carotenoids; Diet; Female; Fruit; Humans; Nutritional Physiological Phenomena; Prognosis; Software; Surveys and Questionnaires; Survival Analysis; Time Factors; Vitamins

Although it has been hypothesized that large intakes of the antioxidant vitamins C, E, and A reduce the risk of breast cancer, few prospective data are available.. We prospectively studied 89,494 women who were 34 to 59 years old in 1980 and who did not have cancer. Their intakes of vitamins C, E, and A from foods and supplements were assessed at base line and in 1984 with the use of a validated semiquantitative food-frequency questionnaire.. Breast cancer was diagnosed in 1439 women during eight years of follow-up. After multivariate adjustment for known risk factors, the relative risk among women in the highest quintile group for intake of vitamin C as compared with the risk among those in the lowest quintile group was 1.03 (95 percent confidence interval, 0.87 to 1.21); for vitamin E, after vitamin A intake had been controlled for, the relative risk was 0.99 (95 percent confidence interval, 0.83 to 1.19). In contrast, among women in the highest quintile group for intake of total vitamin A the relative risk was 0.84 (95 percent confidence interval, 0.71 to 0.98; P for trend = 0.001). Among women in the lowest quintile group for intake of vitamin A from food, consumption of vitamin A from supplements was associated with a reduced risk (P = 0.03). The significant inverse association of vitamin A intake with the risk of breast cancer was also found on study of data based on the 1984 questionnaire and four years of follow-up.. Large intakes of vitamin C or E did not protect women in our study from breast cancer. A low intake of vitamin A may increase the risk of this disease; any benefit of vitamin A supplements may be limited to women with diets low in vitamin A.

Topics: Adult; Ascorbic Acid; Breast Neoplasms; Diet; Feeding Behavior; Female; Follow-Up Studies; Humans; Incidence; Middle Aged; Prospective Studies; Risk Factors; Vitamin A; Vitamin E

Risk of breast cancer was examined in relation to intake of dietary fiber and vitamins A, C, and E, and food groups which are sources of these dietary constituents, in a cohort of 56,837 women enrolled in the Canadian National Breast Screening Study. Between 1982 and 1987, 519 incident, histologically confirmed cases of breast cancer were identified among women who previously had completed self-administered dietary questionnaires. Their nutrient and food intake was compared with that of 1,182 women who had not developed breast cancer during the follow-up period. Women at the uppermost quintile level of dietary fiber intake had a 30 percent reduction in risk of breast cancer relative to that for women at the lowest quintile level (adjusted odds ratio = 0.68, 95 percent confidence interval = 0.46-1.00), and the reduction in risk persisted after adjustment (separately) for total vitamin A, beta-carotene, vitamin C, and alpha-tocopherol. Inverse associations of similar magnitude were observed in association with consumption of pasta, cereals (the trend for which was statistically significant), and vegetables rich in vitamins A and C. Smaller, statistically nonsignificant reductions in risk were observed with increasing intake of dietary retinol, beta-carotene, and vitamin C, but the magnitude of these associations was reduced after adjustment for other dietary factors. Vitamin E intake was not associated with altered risk of breast cancer.

Topics: Ascorbic Acid; Breast Neoplasms; Cohort Studies; Dietary Fiber; Female; Humans; Risk Factors; Vitamin A; Vitamin E; Vitamins

Topics: Ascorbic Acid; Breast Neoplasms; Cholecalciferol; Fatty Acids; Feeding Behavior; Female; Humans; Neoplasms; Nutritional Requirements; Risk Factors; Vitamin A

Relationships between dietary nutrients and plasma prolactin concentration were studied in 249 women with a history of nonskin cancers among first-degree female relatives. For each quintile of nutrient density, the odds ratio (OR), relative to the lowest quintile, of having an elevated (above the median) prolactin concentration was estimated by logistic regression, taking into account parity, menopausal status, and current tobacco-smoking habits. For nutrient densities estimated from 24-h recall data there was a significant positive association between plasma prolactin concentration and increasing saturated fatty acid intake; the OR of elevated prolactin in the top quintile was 3.1 [95% confidence interval (CI) 1.2-8.1] and there was a negative association with vitamin C [OR in the top quintile 0.28, (95% CI 0.10-0.78)]. For usual nutrient densities (estimated by quantitative food frequency questionnaire) there was a statistically significant trend (P = 0.04) toward lower prolactin concentrations with increasing sodium density, and a marginally significant positive trend (P = 0.07) with increasing dietary density of refined sugars.

Topics: Adult; Aged; Ascorbic Acid; Breast Neoplasms; Diet; Dietary Fats; Estrogens; Fatty Acids; Female; Humans; Menopause; Middle Aged; Niacin; Parity; Prolactin; Smoking

Risk factors for fibroadenoma were examined in a case-control study involving 117 fibroadenoma cases ascertained by a major private pathology laboratory in Adelaide, Australia, between January 1983 and October 1985. For each case a population control was randomly selected from the electoral roll in Adelaide and matched to the corresponding case by sex, age, and socioeconomic grading of area of residence. Another 189 women whose first biopsy for benign breast disease was examined in the same laboratory during the same time period as those of the cases, but did not show evidence of epithelial proliferation, were also included in the study as a biopsy control group. Risk of fibroadenoma was associated inversely with the Quetelet index, but there was no evidence of an association with age at menarche or menopausal status. The risk of fibroadenoma decreased with an increasing number of full-term pregnancies and was increased in association with use of oral contraceptives at an early age (under 20 years); however, these two associations were observed only when cases were compared with the population controls. Alcohol consumption and dietary fat intake were found not to be associated with altered risk of fibroadenoma, while in multivariate analyses, duration of cigarette smoking and daily vitamin C intake were both shown to have inverse associations with risk of fibroadenoma. Although fibroadenoma does share some risk factors with breast cancer, there is insufficient evidence to suggest that it represents a precursor state.

Topics: Adenofibroma; Adult; Age Factors; Ascorbic Acid; Biopsy; Body Mass Index; Breast Feeding; Breast Neoplasms; Case-Control Studies; Contraceptives, Oral; Diet Surveys; Female; Humans; Logistic Models; Menopause; Middle Aged; Parity; Risk Factors; Smoking; South Australia

Blood levels of selenium, zinc, copper, and vitamins E and C were measured in 48 cases and 50 controls from a hospital-based case-control study bearing on breast cancer risk factors in Montpellier (France). Cellular levels of selenium and vitamins E and C were also evaluated in most of the subjects. We found that the blood and cellular levels of these antioxidants were overall higher in cases than in controls, significantly for serum zinc, plasma, and leukocyte vitamin E. The statistical significance of the difference between case and control serum Cu crude levels disappeared after adjustment for metabolically related variables. The difference was borderline significant for leukocyte vitamin C. These results were slightly modified when vitamin pill users were excluded from case and control samples. The serum zinc odds ratios computed after adjustment for related variables were significantly elevated (2.53, confidence interval: 1.34-4.78, for the highest tertile) as were those computed previously for pooled plasma vitamin E levels in a joint study.

Topics: Adult; Ascorbic Acid; Breast Neoplasms; Case-Control Studies; Copper; Female; France; Humans; Middle Aged; Selenium; Vitamin E; Zinc

Topics: Acetylcysteine; Ascorbic Acid; Breast Neoplasms; Cell Division; Glutathione; Humans; Saccharomyces cerevisiae; Tamoxifen; Tumor Cells, Cultured

Ascorbic acid, cysteine, glutathione and uric acid were determined by reverse-phase high-pressure liquid chromatography (HPLC) in 46 breast tissue samples [neoplastic (C) and non-neoplastic (N) from the same patient]. Cholesterol, alpha-tocopherol and gamma-tocopherol were quantified in 64 similar samples by extraction into heptane followed by direct-phase HPLC. DNA was measured in all samples and the percentages of epithelium, fat and connective tissue were estimated in sections adjacent to the sample. Results confirm previous findings that ascorbic acid and glutathione, expressed as mumol/g DNA, were greatly increased in the epithelium of neoplastic tissue. Similar increases in cysteine could be accounted for by the presence of inflammatory cells. Although values of alpha- and gamma-tocopherol correlated with the percentage of fat in both types of tissue, these compounds were also present in the epithelium. Because of the varying amounts of fat in the samples, no significant difference could be found between N and C values. Cholesterol correlated with fat in N and epithelium in C. Consideration of 10 cases with equal amounts of fat in C and N tissue suggests that cholesterol is reduced in C in the epithelial cells.

Topics: Antioxidants; Ascorbic Acid; Breast; Breast Neoplasms; Cholesterol; Chromatography, High Pressure Liquid; Cysteine; DNA; DNA, Neoplasm; Epithelium; Female; Glutathione; Humans; Solubility; Uric Acid; Vitamin E

The effects of sodium ascorbate (vitamin C) and 2-methyl-1,4-naphthoquinone (vitamin K3) administered separately or in combination on the in vitro cultured human neoplastic cell lines MCF-7 (breast carcinoma), KB (oral epidermoid carcinoma), and AN3-CA (endometrial adenocarcinoma) have been examined. When given separately, vitamin C or K3 had a growth inhibiting action only at high concentrations (5.10(3) mumol/1 and 10(5) nmol/l, respectively). Combined administration of both vitamins demonstrated a synergistic inhibition of cell growth at 10 to 50 times lower concentrations. At this level separately given vitamins are not toxic. The sensitivity to this treatment was somewhat different in the three cell lines, being slightly higher for KB line. This tumor cell growth inhibitory effect was completely suppressed by the addition of catalase to the culture medium containing vitamins C and K3, suggesting an excessive production of hydrogen peroxide as being implied in mechanisms responsible for the above-mentioned effects.

Topics: Adenocarcinoma; Ascorbic Acid; Breast Neoplasms; Carcinoma, Squamous Cell; Catalase; Cell Division; Drug Synergism; Female; Humans; Mouth Neoplasms; Tumor Cells, Cultured; Uterine Neoplasms; Vitamin K

The water-soluble scavengers ascorbic acid (Asc), cysteine (Cys), glutathione (GSH) and uric acid (UA) as well as DNA content were determined in 40 breast tissue samples (neoplastic and non-neoplastic tissues from 20 patients). To allow proper homogenization to take place, a fixed number of sections was cut from a tissue cylinder of known diameter. Adjacent sections were stained with hematoxylin-eosin and the fractions of epithelium, fat and connective tissue were estimated as a percentage of the section area. Protein-free extracts were injected into a reverse-phase high-pressure liquid chromatography system and scavengers quantified with 2 electrochemical detectors (gold and glassy carbon). DNA and all scavengers, except UA, were greatly increased in cancer tissues in nearly all cases. Amounts of Asc and GSH in neoplastic tissue correlated closely with DNA values and percentage of epithelium, those of Cys not so closely and those of UA not at all. We assume that Asc and GSH were located mainly in the epithelium, UA mainly in the extracellular space and Cys in both spaces. When values were expressed as mumol/g DNA, a parameter related to content per cell, values were higher in neoplastic than in non-neoplastic tissue for Asc (18/20 cases), GSH (17/20) and Cys (14/20) and lower in neoplastic tissue for UA (19/20). It is known that increased GSH protects cells against certain drugs in tissue cultures. For in vivo treatment the presence of increased Asc (and to a lesser extent Cys) in addition to GSH could be of importance.

Topics: Adult; Aged; Aged, 80 and over; Ascorbic Acid; Breast; Breast Neoplasms; Chromatography, High Pressure Liquid; Cysteine; DNA; Epithelium; Extracellular Space; Female; Glutathione; Humans; Middle Aged; Uric Acid

Topics: Antineoplastic Combined Chemotherapy Protocols; Ascorbic Acid; Breast Neoplasms; Female; Humans

Estrogen receptor (ER) and progesterone receptor (PgR) were measured by sucrose gradient centrifugation before and after various therapies, such as radiation, chemotherapy and hormone therapy. The subjects were 18 advanced or recurrent human breast cancers and 51 DMBA-induced mammary tumors of female SD rats. Changes of hormone receptors and the relationship between receptor levels and the effects of the therapies were examined. Changes of tumor cellularity were also studied in human breast cancers. Some ER-positive tumors changed into ER-negative and others did not. Most ER-negative tumors did not change in ER status. In the responsive cases, receptor levels tended to decline more remarkably and the cellularity of human breast cancer decreased.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Adult; Aged; Animals; Antineoplastic Combined Chemotherapy Protocols; Ascorbic Acid; Breast Neoplasms; Combined Modality Therapy; Cyclophosphamide; Doxorubicin; Female; Fluorouracil; Humans; Mammary Neoplasms, Experimental; Medroxyprogesterone; Medroxyprogesterone Acetate; Middle Aged; Rats; Receptors, Estrogen; Receptors, Progesterone

The effects of vitamin C on the growth of human lung cultures and of vitamin C or L-cysteine on a human breast cancer culture (SK-Br-3) were assessed with and without exposure to fresh smoke from tobacco or marijuana cigarettes. When grown in the presence of vitamin C, lung cultures exposed or not exposed to either type of smoke showed a stimulation of growth and a significant decrease in mitotic abnormalities. However, abnormalities were much more marked in marijuana-exposed cultures than in tobacco-smoke-exposed ones. Nonexposed or tobacco-smoke-exposed breast cancer cultures, when grown in the presence of vitamin C, also showed acceleration of growth of epithelial cells, significant reduction in mitotic abnormalities, and occurrence of pseudoglandular structures, indicating differentiation. These alterations not only disappeared, but the cultures also became fibroblastic when they were returned to media without vitamin C. In contrast, vitamin C did not reduce mitotic abnormalities in marijuana-smoke-exposed breast cancer cultures, but stimulated abnormal growth and dedifferentiation. In nonexposed, tobacco-, or marijuana-smoke-exposed breast cancer cultures. L-cysteine evoked an acceleration of fibroblastic growth, which was not altered when the cultures were returned to media without L-cysteine.

Topics: Adult; Ascorbic Acid; Breast Neoplasms; Cannabis; Cell Line; Cells, Cultured; Cysteine; DNA; Female; Fetus; Humans; Lung; Nicotiana; Plants, Toxic; Pregnancy; Smoke

The effect of long term ascorbic acid (AA) supplementation (3g per day) on 27 women with early breast cancer has been investigated. For comparison a similar but limited study was carried out in patients with benign breast disease. The responses of leucocyte levels of AA to supplementation provided some evidence to suggest that the metabolism and utilisation of the vitamin may be different in these patients. In addition longitudinal measurements of urinary hydroxyproline/creatinine (OHPro/Cr) ratio were carried out in these patients. The long term ingestion of AA did not appear to affect the prognosis of the disease in the early breast cancer group. Similar 5 year survival rates were seen in the unsupplemented and supplemented cancer groups.

Topics: Adult; Aged; Ascorbic Acid; Breast Diseases; Breast Neoplasms; Creatinine; Female; Humans; Hydroxyproline; Longitudinal Studies; Middle Aged; Neoplasm Recurrence, Local; Prognosis

There are substantial data on breast tumorigenesis in animals that suggest that diet may be an important factor in human breast cancer etiology. The promotional effects of dietary fat, and, in particular, unsaturated fats, on mammary tumors in rodents is well established. The geographic distribution of breast cancer in humans correlates with international differences in average fat intake. Differences in dietary habits among populations in the United States and their breast cancer risk also have been observed. In the United States, the trend has been toward increased total fat consumption and increased use of polyunsaturated fats. However, breast cancer incidence among white women in the United States has changed very little. Case-control studies of dietary intake and breast cancer risk have shown inconsistent results, and prospective studies of breast cancer mortality and serum cholesterol and serum lipids show no differences in risk between women with high levels of cholesterol and serum lipids compared with women with low levels. Laboratory studies also suggest the possibility that natural inhibitors of breast cancer may occur in the diet as well. Antioxidants, inducers of microsomal enzyme activity, and retinoids, all have been implicated in the metabolic epidemiology of breast cancer. Research results at Roswell Park memorial Institute have associated lower levels of intake of dietary vitamin A with a slightly elevated risk of breast cancer. To date, the epidemiologic data do not indicate with confidence that any specific dietary risk factor may be associated with breast cancer risk in the United States population. Additional epidemiologic studies on inhibition or promotion of breast cancer following the leads of previous laboratory research may clarify the nature and practical significance of the relationship between diet and breast cancer.

Topics: Adolescent; Adult; Animals; Antioxidants; Ascorbic Acid; Breast Neoplasms; Child; Cholesterol; Diet; Dietary Fats; Fats, Unsaturated; Feeding Behavior; Female; Humans; Lipids; Mammary Neoplasms, Experimental; Mice; Middle Aged; Rats; Retrospective Studies; Risk; United States; Vitamin A

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Ascorbic Acid; Breast Neoplasms; Female; Humans; Methotrexate; Time Factors

Topics: Animals; Ascorbic Acid; Breast Neoplasms; Fluorouracil; Humans; Lung Neoplasms; Mice; Neoplasms; Neoplasms, Experimental; Orthomolecular Therapy; Thiamine; Thiamine Pyrophosphate; Transketolase; Vitamin A

Incidence rates for many sites of cancer show wide variations among the main ethnic groups in Hawaii (Caucasians, Japanese, Chinese, Filipinos, and Hawaiians). Major shifts in cancer rates among migrants to the islands suggest that environmental factors are at least in part responsible for these variations. One prominent area of difference among these ethnic populations is their diets, which can vary substantially, not only in the consumption of particular food items but also in mean nutrient intakes. In aggregate correlational analyses based on data from representative samples of these ethnic groups and corresponding population-based cancer incidence rates, we found significant associations between ethnic-sex-specific intakes of dietary fat (including total fat, as well as animal, saturated, and unsaturated fats) and breast, endometrial, and prostate cancers. Animal protein intake showed associations similar to those for dietary fat, but these two nutrients were highly correlated in the data. Cholesterol intake showed significant correlations with lung and laryngeal cancers. Analyses of both nutrient and food item data suggested an association of stomach cancer incidence with the consumption of fish products, particularly dried/salted fish, and with a lower intake of vitamin C. Preliminary findings from ongoing case-control studies showed the following relationships: an inverse association between lung cancer risk and the intake of food sources of vitamin A, especially foods containing carotenes; an inverse association between cancers of the lower urinary tract and vitamin A consumption, especially from supplements; a positive association between prostate cancer risk and dietary fat intake in men above age 69, but not in younger men; and a positive association between breast cancer risk and the intake of dietary fat (particularly saturated fat) and animal protein in postmenopausal women, especially the Japanese. Two large cohorts (50,000 and 5,000 subjects) on whom dietary information was collected between 1975 and 1980 are being followed prospectively for their occurrence of cancer.

Topics: Age Factors; Aged; Ascorbic Acid; Breast Neoplasms; Diet; Dietary Fats; Ethnicity; Female; Hawaii; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasms; Prostatic Neoplasms; Risk; Urologic Neoplasms; Vitamin A

A variety of studies have shown that diets high in fat, particularly polyunsaturated, have enhanced the production of tumors in animals challenged with chemical carcinogens. Other studies have found an apparent contradiction of no difference in the incidence of breast cancer among women with varying levels of serum cholesterol as measured decades earlier. The present study concerns 2024 breast cancer cases and 1463 control patients without neoplasms or pathology of the reproductive and digestive organs, seen at Roswell Park Memorial Institute from 1958 to 1965. Based upon the assessments of their varying ingestion of fats from their own reports of diets, no difference in risk was found. Similarly, there was no difference in risk of breast cancer associated with ingesting diets containing various levels of either vitamin C or the cruciferous vegetables. Risk for breast cancer in women 55 years of age and older increased somewhat with decreases in ingestion of foods containing vitamin A.

Topics: Aging; Ascorbic Acid; Breast Neoplasms; Data Collection; Diet; Dietary Fats; Epidemiologic Methods; Female; Humans; Middle Aged; New York; Risk; Vegetables; Vitamin A

Present evidence suggests that a high fat intake may be one of the factors in the aetiology of breast cancer. Patients with breast cancer may show an increased requirement for thiamin particularly when treated with 5-fluorouracil, and a number of metabolic disturbances in which ascorbic acid may play a central role.

Topics: Animals; Ascorbic Acid; Bone Neoplasms; Breast Neoplasms; Calcium; Dietary Fats; Feeding Behavior; Female; Fluorouracil; Humans; Hydroxyproline; Lipase; Lipids; Mammary Neoplasms, Experimental; Mice; Neoplasm Metastasis; Rats; Thiamine Deficiency; Thiamine Pyrophosphate

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Breast Neoplasms; Female; Humans; Hydroxyproline; Lipid Metabolism; Neoplasm Metastasis; Neoplasms; Thiamine Deficiency; Vitamin A; Vitamin A Deficiency

Topics: Adult; Ascorbic Acid; Breast Neoplasms; Child; Female; Humans; Leukocytes; Lung Neoplasms; Mouth Neoplasms; Neoplasms; Rectal Neoplasms; Skin Neoplasms; Urinary Bladder Neoplasms; Uterine Cervical Neoplasms

Ascorbic acid metabolism is associated with a number of mechanisms known to be involved in host resistance to malignant disease. Cancer patients are significantly depleted of ascorbic acid, and in our opinion this demonstrable biochemical characteristic indicates a substantially increased requirement and utilization of this substance to potentiate these various host resistance factors. The results of a clinical trial are presented in which 100 terminal cancer patients were given supplemental ascorbate as part of their routine management. Their progress is compared to that of 1000 similar patients treated identically, but who received no supplemental ascorbate. The mean survival time is more than 4.2 times as great for the ascorbate subjects (more than 210 days) as for the controls (50 days). Analysis of the survival-time curves indicates that deaths occur for about 90% of the ascorbate-treated patients at one-third the rate for the controls and that the other 10% have a much greater survival time, averaging more than 20 times that for the controls. The results clearly indicate that this simple and safe form of medication is of definite value in the treatment of patients with advanced cancer.

Topics: Adult; Aged; Ascorbic Acid; Breast Neoplasms; Bronchial Neoplasms; Colonic Neoplasms; Female; Humans; Kidney Neoplasms; Male; Middle Aged; Neoplasms; Ovarian Neoplasms; Rectal Neoplasms; Stomach Neoplasms; Terminal Care; Urinary Bladder Neoplasms

Topics: Aged; Ascorbic Acid; Breast Neoplasms; Chromatography, Gas; Chromatography, Thin Layer; Estradiol; Estriol; Estrone; Female; Humans; Menopause; Methods

Topics: Age Determination by Skeleton; Ascorbic Acid; Breast Neoplasms; Collagen; Female; Humans; Hydroxyproline; Leukocytes; Male; Neoplasm Metastasis

Topics: Administration, Oral; Ascorbic Acid; Breast Neoplasms; Carcinoma; Colonic Neoplasms; Dose-Response Relationship, Drug; Drug Evaluation; Drug Stability; Female; Fibrosarcoma; Humans; Injections, Intravenous; Neoplasms; Papilloma; Rectal Neoplasms; Stomach Neoplasms; Time Factors; Urinary Bladder Neoplasms

Topics: Ascorbic Acid; Bone Neoplasms; Breast Neoplasms; Female; Humans; Hydroxyproline; Leukocytes; Male; Neoplasm Metastasis; Time Factors

Topics: Adenocarcinoma; Ascorbic Acid; Bone Neoplasms; Breast Neoplasms; Humans; Neoplasm Metastasis

Topics: Adenocarcinoma; Aged; Animals; Ascorbic Acid; Biological Assay; Breast Neoplasms; Child; Child, Preschool; Female; Humans; Hypophysectomy; Luteinizing Hormone; Male; Ovary; Rats

Topics: Adenoma, Chromophobe; Ascorbic Acid; Breast Neoplasms; Choriocarcinoma; Chorionic Gonadotropin; Female; Hemagglutination Inhibition Tests; Humans; Immune Sera; Luteinizing Hormone; Menopause; Middle Aged; Pituitary Neoplasms; Pregnancy; Uterine Neoplasms

Topics: Ascorbic Acid; Blood Transfusion; Brazil; Breast Neoplasms; Cyclophosphamide; Female; Humans; Neoplasms; Ovarian Neoplasms; Thyroid Hormones; Urethral Neoplasms; Uterine Cervical Neoplasms; Vaginal Neoplasms; Vitamin B 12; Vitamin B Complex

Topics: Animals; Ascorbic Acid; Breast; Breast Neoplasms; Dairy Products; Humans; Mice; Milk; Neoplasms, Experimental

Topics: Ascorbic Acid; Breast Neoplasms; Cells; Glutathione; Humans; Neoplasms