ascorbic-acid and Prostatic-Neoplasms

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

The purpose of this review is to examine the evidence on the effects of bioactive constituents of the Mediterranean diet (MeDi) on prostate cancer (PCa) risk.. The search for articles came from extensive research in the following databases: PubMed, Scopus, and Web of Science. We used the search terms "Mediterranean diet," "lycopene," "vitamin E," "vitamin C," "Selenium," "resveratrol," "prostate cancer," and combinations, such as "lycopene and prostate cancer" or "resveratrol and prostate cancer.". Numerous studies investigating the effect of various dietary nutrients on PCa have suggested that selenium is probably the most promising. Several studies reported reduced PCa risk associated with vitamin C and E intake, while other studies reported no association. Lycopene inhibits cell proliferation and inducts apoptosis, thus protecting against cancer. Also, it has been found in various in vivo and in vitro studies that resveratrol, inhibits PCa development.. The high content of bioactive phytochemicals in the MeDi is of particular interest in the prevention of PCa. Further large-scale studies are required to clarify the effect of MeDi bioactive compounds on prostate health, in order to establish the role of this diet in the prevention of PCa.

Topics: Anticarcinogenic Agents; Ascorbic Acid; Diet, Mediterranean; Humans; Lycopene; Male; Phytochemicals; Prostatic Neoplasms; Risk Factors; Vitamin E; Vitamins

Prostate cancer is the most common noncutaneous cancer in men in the United States. Several studies have examined the relationship between prostate cancer and antioxidants; however, the results of these studies are inconsistent. This article provides a systematic review of studies on prostate cancer and antioxidant intake from diet and supplements. Tea and coffee appear to offer protection against advanced prostate cancer. Different forms of vitamin E appear to exert different effects on prostate cancer, with alpha-tocopherol potentially increasing and gamma-tocopherol potentially decreasing risk of the disease. There is no strong evidence for a beneficial effect of selenium, vitamin C, or beta-carotene, whereas lycopene appears to be negatively associated with risk of the disease. The effect of dietary antioxidants on prostate cancer remains undefined and inconclusive, with different antioxidants affecting prostate cancer risk differentially. Further studies are needed to clarify the relationship between antioxidants and prostate cancer risk and to delineate the underlying mechanisms.

Topics: alpha-Tocopherol; Antioxidants; Ascorbic Acid; beta Carotene; Carotenoids; Coffee; Diet; Dietary Supplements; gamma-Tocopherol; Humans; Lycopene; Male; Polyphenols; Prostatic Neoplasms; Randomized Controlled Trials as Topic; Risk Factors; Selenium; Tea; United States

Vitamin supplementation is used for many purposes with mainly alleged benefits. One of these is the use of various vitamins for the prevention of prostate cancer.. We conducted a systematic review and meta-analysis on this topic. Pubmed, Embase and the Cochrane Database were searched; as well, we hand searched the references in key articles. Randomized controlled trials (RCTs), cohort studies and case-control studies were included. The review assessed the effect of supplemental vitamins on the risk of prostate cancer and on disease severity and death in men with prostate cancer.. Fourteen articles were included in the final assessment. Individually, a few of these studies showed a relationship between the ingestion of supplemental vitamins or minerals and the incidence or severity of prostate cancer, especially in smokers. However, neither the use of multivitamin supplementation nor the use of individual vitamin/mineral supplementation affected the overall occurrence of prostate cancer or the occurrence of advanced/metastatic prostate cancer or death from prostate cancer when the results of the studies were combined in a meta-analysis. We also conducted several sensitivity analyses by running meta-analysis using just the higher quality studies and just the RCTs. There were still no associations found.. There is no convincing evidence that the use of supplemental multivitamins or any specific vitamin affects the occurrence or severity of prostate cancer. There was high heterogeneity among the studies so it is possible that unidentified subgroups may benefit or be harmed by the use of vitamins.

Topics: Ascorbic Acid; beta Carotene; Dietary Supplements; Humans; Male; Minerals; Prostatic Neoplasms; Selenium; Vitamin E; Vitamins; Zinc

Several studies have evaluated the possible association between antioxidants vitamins or selenium supplement and the risk of prostate cancer, but the evidence is still inconsistent. We systematically searched PubMed, EMBASE, the Cochrane Library, Science Citation Index Expanded, Chinese biomedicine literature database, and bibliographies of retrieved articles up to January 2009. We included 9 randomized controlled trials with 165,056 participants; methodological quality of included trials was generally high. Meta-analysis showed that no significant effects of supplementation with beta-carotene (RR 0.97, 95% CI 0.90-1.05) (3 trials), vitamin C (RR 0.98, 95% CI 0.91-1.06) (2 trials), vitamin E (RR 0.96, 95% CI 0.85-1.08) (5 trials), and selenium (RR 0.78, 95% CI 0.41-1.48) (2 trials)versus placebo on prostate cancer incidence. The mortality of prostate cancer did not differ significantly by supplement of beta-carotene (RR 1.19, 95% CI 0.87 -1.65) (1 trial), vitamin C (RR 1.45, 95%CI 0.92-2.29) (1 trial), vitamin E (RR 0.85, 95%CI 0.58-1.24) (2 trials), and selenium (RR 2.98, 95% CI 0.12-73.16) (1 trial). Our findings indicate that antioxidant vitamins and selenium supplement did not reduce the incidence and mortality of prostate cancer, these data provide no support for the use of these supplements for the prevention of prostate cancer.

Topics: Adult; Aged; Antioxidants; Ascorbic Acid; beta Carotene; Dietary Supplements; Humans; Male; Middle Aged; Prostatic Neoplasms; Randomized Controlled Trials as Topic; Selenium; Vitamin E

Epidemiological studies have shown marked variations in prostate cancer incidence and mortality across different geographic regions, leading to the rising interest in the role of nutrition in prostate cancer risk. There is also a large body of evidence that a diverse diet, rich in vegetables, can reduce the risk of prostate cancer. In this review, the role of various kinds of vegetables and their bioactive compounds associated with prostate cancer risk, and the underlying mechanisms of these associations are summarized. There is accumulating evidence to support the consumption of lycopene, in particular tomato and tomato-based products, as protective factors against prostate cancer. Evidence on the protective role of beta-carotene was inconsistent from cohort and case-control studies. Evidence on the effect of pulses or soy consumption on prostate cancer risk was limited but suggestive of decreased risk with increased pulses or soy consumption. However, the role of vitamin C, vitamin E, allium vegetables, and cruciferous vegetables on prostate cancer risk remains to be determined due to limited evidence. Although the impact on prostate cancer risk differs among various vegetables and their constituent nutrients, the overall benefits of plant based diet on cancer prevention and other diet-related diseases should be promoted.

Topics: Allium; Ascorbic Acid; beta Carotene; Brassicaceae; Carotenoids; Diet; Flavonoids; Humans; Lycopene; Male; Prostatic Neoplasms; Vegetables

Prostate cancer is the second leading cause of cancer deaths among men. It is common in Australia, New Zealand, North America and North West Europe, but rare in Asia, Africa and South America.. This article reviews the role of chemopreventive agents for prostate cancer. The available evidence strongly suggests that dietary changes and supplementation with a variety of micronutrients, vitamins and trace elements may reduce the incidence and mortality of prostate cancer.. Epidemiologic observations reveal lower cancer rates in those with diets rich in fruits, vegetables, vitamins, and a number of specific foods. This available data is adequate to clinically apply the role of various factors to possibly reduce the incidence of prostate cancer.

Topics: Adult; Aged; Aged, 80 and over; Androgen Antagonists; Ascorbic Acid; Complementary Therapies; Dietary Supplements; Health Behavior; Humans; Male; Middle Aged; Phytotherapy; Plant Extracts; Prostatic Neoplasms; Risk Factors; Selenium; Serenoa; Soy Foods; Tea; Vitamin E

Topics: Antioxidants; Ascorbic Acid; Carotenoids; Diet; Dietary Fats; Estrogens, Non-Steroidal; Humans; Isoflavones; Male; Meat; Phytoestrogens; Plant Preparations; Plants; Prostatic Neoplasms; Selenium; Tocopherols; Vitamin A; Vitamin D; Vitamin E

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

Topics: Animals; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Ascorbic Acid; Humans; Male; Prostatic Neoplasms; Vitamin K

CANCER OF THE PROSTATE AND VITAMINS: Four vitamins have been studied, vitamins A, E, D and C. the results of these studies have been contradictory. Vitamin A and vitamin E would have a protective effect. ANTIOXIDANTS: Carotenes have an activity similar to that of vitamin A. Beta-carotene was positively associated with risk of cancer of the prostate in one study while two others were unable to demonstrate any relationship. Lycopene, the red color in fruits and vegetables, particularly tomatoes, would contribute to a lower risk of prostate cancer.. Cadmium would increase the risk of cancer while selenium would have a protective effect. However studies concerning selenium carry certain methodological biases.

Topics: Aged; Animals; Antioxidants; Ascorbic Acid; beta Carotene; Cadmium; Carotenoids; Clinical Trials as Topic; Cohort Studies; Follow-Up Studies; Humans; Lycopene; Male; Mice; Prospective Studies; Prostatic Neoplasms; Randomized Controlled Trials as Topic; Risk Factors; Selenium; Solanum lycopersicum; Time Factors; Trace Elements; Tumor Cells, Cultured; Vitamin A; Vitamin D; Vitamin E; Vitamins

Topics: Ascorbic Acid; Carotenoids; Developed Countries; Epidemiologic Studies; Fruit; Humans; Male; Prostatic Neoplasms; Risk Factors; Vegetables; Vitamin E

Treatment with high-dose intravenous (IV) ascorbic acid (AA) is used in complementary and alternative medicine for various conditions including cancer. Cytotoxicity to cancer cell lines has been observed with millimolar concentrations of AA. Little is known about the pharmacokinetics of high-dose IV AA. The purpose of this study was to assess the basic kinetic variables in human beings over a relevant AA dosing interval for proper design of future clinical trials. Ten patients with metastatic prostate cancer were treated for 4 weeks with fixed AA doses of 5, 30 and 60 g. AA was measured consecutively in plasma and indicated first-order elimination kinetics throughout the dosing range with supra-physiological concentrations. The target dose of 60 g AA IV produced a peak plasma AA concentration of 20.3 mM. Elimination half-life was 1.87 hr (mean, S.D. ± 0.40), volume of distribution 0.19 L/kg (S.D. ±0.05) and clearance rate 6.02 L/hr (100 mL/min). No differences in pharmacokinetic parameters were observed between weeks/doses. A relatively fast first-order elimination with half-life of about 2 hr makes it impossible to maintain AA concentrations in the potential cytotoxic range after infusion stop in prostate cancer patients with normal kidney function. We propose a regimen with a bolus loading followed by a maintenance infusion based on the calculated clearance.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Area Under Curve; Ascorbic Acid; Half-Life; Humans; Male; Middle Aged; Neoplasm Metastasis; Prostatic Neoplasms; Vitamins

Recent posttrial analysis of a completed randomized trial found an increased risk of prostate cancer among healthy men taking high-dose vitamin E supplements. Trials that examined the effect of vitamin C supplements on cancer risk are few.. We examined whether vitamin E or vitamin C supplementation affects the risk of cancer events during posttrial follow-up of the Physicians' Health Study II.. Beginning in 1997, a total of 14,641 US male physicians aged ≥50 y were randomly assigned to receive 400 IU of vitamin E every other day, 500 mg of vitamin C daily, or their respective placebos. The vitamin E and vitamin C treatment ended in 2007, and observational follow-up continued through June 2011.. This study included an additional 356 cases of incident prostate cancer and 771 total cancers that developed during a mean (maximum) of 2.8 (3.8) y of posttrial observation. During an overall mean of 10.3 (13.8) y, there were a total of 1373 incident prostate cancers and 2669 total cancers documented. In comparison with placebo, vitamin E supplementation had no effect on the incidence of prostate cancer (HR: 0.99; 95% CI: 0.89, 1.10) or total cancers (HR: 1.02; 95% CI: 0.95, 1.10). There was also no effect of vitamin C supplementation on total cancers (HR: 1.02; 95% CI: 0.94, 1.10) or incident prostate cancer (HR: 1.03; 95% CI: 0.93, 1.15). Neither vitamin E nor vitamin C supplementation had effects on other site-specific cancers overall. Stratification by known cancer risk factors, history of cancer, other randomized treatment, and follow-up time showed no significant interactions.. In this large-scale randomized trial in men, vitamin E and C supplementation had no immediate or long-term effects on the risk of total cancers, prostate cancer, or other site-specific cancers.

Topics: Aged; Antioxidants; Ascorbic Acid; Cohort Studies; Dietary Supplements; Double-Blind Method; Follow-Up Studies; Humans; Incidence; Male; Middle Aged; Neoplasms; Physicians; Prostatic Neoplasms; Risk Factors; United States; Vitamin E

Many individuals take vitamins in the hopes of preventing chronic diseases such as cancer, and vitamins E and C are among the most common individual supplements. A large-scale randomized trial suggested that vitamin E may reduce risk of prostate cancer; however, few trials have been powered to address this relationship. No previous trial in men at usual risk has examined vitamin C alone in the prevention of cancer.. To evaluate whether long-term vitamin E or C supplementation decreases risk of prostate and total cancer events among men.. The Physicians' Health Study II is a randomized, double-blind, placebo-controlled factorial trial of vitamins E and C that began in 1997 and continued until its scheduled completion on August 31, 2007. A total of 14,641 male physicians in the United States initially aged 50 years or older, including 1307 men with a history of prior cancer at randomization, were enrolled.. Individual supplements of 400 IU of vitamin E every other day and 500 mg of vitamin C daily.. Prostate and total cancer.. During a mean follow-up of 8.0 years, there were 1008 confirmed incident cases of prostate cancer and 1943 total cancers. Compared with placebo, vitamin E had no effect on the incidence of prostate cancer (active and placebo vitamin E groups, 9.1 and 9.5 events per 1000 person-years; hazard ratio [HR], 0.97; 95% confidence interval [CI], 0.85-1.09; P = .58) or total cancer (active and placebo vitamin E groups, 17.8 and 17.3 cases per 1000 person-years; HR, 1.04; 95% CI, 0.95-1.13; P = .41). There was also no significant effect of vitamin C on total cancer (active and placebo vitamin C groups, 17.6 and 17.5 events per 1000 person-years; HR, 1.01; 95% CI, 0.92-1.10; P = .86) or prostate cancer (active and placebo vitamin C groups, 9.4 and 9.2 cases per 1000 person-years; HR, 1.02; 95% CI, 0.90-1.15; P = .80). Neither vitamin E nor vitamin C had a significant effect on colorectal, lung, or other site-specific cancers. Adjustment for adherence and exclusion of the first 4 or 6 years of follow-up did not alter the results. Stratification by various cancer risk factors demonstrated no significant modification of the effect of vitamin E on prostate cancer risk or either agent on total cancer risk.. In this large, long-term trial of male physicians, neither vitamin E nor C supplementation reduced the risk of prostate or total cancer. These data provide no support for the use of these supplements for the prevention of cancer in middle-aged and older men.. clinicaltrials.gov Identifier: NCT00270647.

Topics: Aged; alpha-Tocopherol; Antioxidants; Ascorbic Acid; Dietary Supplements; Double-Blind Method; Humans; Longitudinal Studies; Male; Middle Aged; Neoplasms; Prostatic Neoplasms; Treatment Outcome; Vitamin E

To evaluate the safety and efficacy of oral Apatone (Vitamin C and Vitamin K3) administration in the treatment of prostate cancer in patients who failed standard therapy.. Seventeen patients with 2 successive rises in PSA after failure of standard local therapy were treated with (5,000 mg of VC and 50 mg of VK3 each day) for a period of 12 weeks. Prostate Specific Antigen (PSA) levels, PSA velocity (PSAV) and PSA doubling times (PSADT) were calculated before and during treatment at 6 week intervals. Following the initial 12 week trial, 15 of 17 patients opted to continue treatment for an additional period ranging from 6 to 24 months. PSA values were followed for these patients.. At the conclusion of the 12 week treatment period, PSAV decreased and PSADT increased in 13 of 17 patients (p < or = 0.05). There were no dose-limiting adverse effects. Of the 15 patients who continued on Apatone after 12 weeks, only 1 death occurred after 14 months of treatment.. Apatone showed promise in delaying biochemical progression in this group of end stage prostate cancer patients.

Topics: Administration, Oral; Aged; Ascorbic Acid; Drug Therapy, Combination; Humans; Male; Middle Aged; Prostatic Neoplasms; Salvage Therapy; Vitamin K 3

To assess the effect of a nutritional supplement containing vitamin E, selenium, vitamin C and coenzyme Q10 on changes in serum levels of PSA in patients with hormonally untreated carcinoma of the prostate and rising serum PSA levels.. Eighty patients were randomised to receive a daily supplement with either vitamin E, selenium, vitamin C, coenzyme Q10 (intervention group) or placebo over 21 weeks. Serum levels of PSA were assessed at baseline (-2, -1, 0 weeks) and after 6, 13, 19, 20 and 21 weeks. Mean changes in log serum level of PSA, testosterone, dihydrotestosterone, luteinizing hormone and sex hormone binding globulin over 21 weeks between the verum and the placebo group were compared by analysis of covariance.. Seventy patients completed the study (36 verum; 34 placebo). Compliance was >90% in all patients. In the intervention group, plasma levels of vitamin E, selenium and coenzyme Q10 increased significantly over the 21 weeks study period. No significant differences in serum levels of PSA, testosterone, dihydrotestosterone, luteinizing hormone or sex hormone binding globulin (p>0.2) were observed between the intervention and control group.. Our results indicate that supplementation of a combination of vitamin E, selenium, vitamin C and coenzyme-Q10 does not affect serum level of PSA or hormone levels in patients with hormonally untreated carcinoma of the prostate.

Topics: Aged; Aged, 80 and over; Ascorbic Acid; Coenzymes; Dietary Supplements; Double-Blind Method; Drug Therapy, Combination; Hormones; Humans; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms; Selenium; Ubiquinone; Vitamin E

In vitro exposure of malignant prostate cell lines to ascorbic acid-menadione showed that tumor cells were killed through a mechanism named autoschizis. Experimental animal studies showed that autoschizis is also evident when ascorbic acid-menadione is administered to nude mice with implanted human prostate tumors. Prostate-specific antigen (PSA) is a known serum marker of prostate tumor cells specific activity. Recently, total serum homocysteine has been identified as a marker of tumor cell numbers with sensitivity for early detection of tumor cell death induced by treatments. A clinical trial with prostate cancer patients submitted to the association of ascorbic acid-menadione was performed and PSA/homocysteine was assessed in the follow- up. The early response in serum PSA and homocysteine levels was reported. The results showed that ascorbic acid-menadione produced an immediate drop in tumor cell numbers as assessed by homocysteine levels. Serum PSA levels showed an early rise and later dropped. These results suggest that autoschizis can also be induced by this pharmacological association at the clinical level in prostate cancer patients. Further studies are being performed in order to research if these results can be found with other primary tumors as it was shown in in vitro and experimental models. Ascorbic acid-menadione could be emerging as a new antitumoral chemotherapy.

Topics: Aged; Analysis of Variance; Antineoplastic Combined Chemotherapy Protocols; Ascorbic Acid; Biomarkers, Tumor; Cell Death; Follow-Up Studies; Homocysteine; Humans; Male; Middle Aged; Prospective Studies; Prostate-Specific Antigen; Prostatic Neoplasms; Treatment Outcome; Vitamin K 3

We propose a hypothesis that differences in base excision repair capacity modulate the effect of dietary antioxidant intake on prostate cancer risk. As a preliminary test of this hypothesis, we conducted a pilot case-control study to evaluate prostate cancer risk in men with polymorphisms in the XRCC1 gene, a key player in base excision repair, across different strata of antioxidant intake. Seventy-seven prostate cancer patients and 183 community controls, for whom we have detailed dietary information, were frequency matched on age and race. We found a somewhat lower prostate cancer risk for men with one or two copies of the variant alleles at the XRCC1 codons 194 and 399 than for those who were homozygous for the common allele [codon 194: odds ratio (OR) = 0.8; 95% confidence interval (CI), 0.4-1.8 and codon 399: OR = 0.8; 95% CI, 0.5-1.3]. The variant at codon 280 was associated with a slightly increased prostate cancer risk (OR = 1.5; 95% CI, 0.7-3.6). Only the codon 399 polymorphism occurred frequently enough to investigate its joint effect with antioxidant intake. Prostate cancer risk was highest among men who were homozygous for the common allele at codon 399 and had low dietary intake of vitamin E (OR = 2.4; 95% CI, 1.0-5.6) or lycopene (OR = 2.0; 95% CI, 0.8-4.9), whereas low intake of these antioxidants in men without this genotype hardly increased prostate cancer risk. The polymorphism did not modulate risk associated with low intake of vitamin C, A, or beta-carotene. The data give some support for our hypothesis but should be regarded as preliminary, because it is limited by small sample size. We discuss what kind of data and what kind of studies are needed for future evaluation of this hypothesis.

Topics: Aged; Antioxidants; Ascorbic Acid; beta Carotene; Carotenoids; Case-Control Studies; Codon; DNA Repair; DNA-Binding Proteins; Eating; Follow-Up Studies; Gene Frequency; Genotype; Humans; Lycopene; Male; Middle Aged; Neoplasm Staging; Pilot Projects; Polymorphism, Genetic; Prostatic Neoplasms; Risk Factors; Treatment Outcome; Vitamin E; X-ray Repair Cross Complementing Protein 1

Low serum cholesterol has been associated with an increased risk of cancer mortality in various studies, which has led to uncertainty regarding the benefit of lower blood cholesterol.. The aim of our study was to evaluate the association between low blood cholesterol (<5.16 mmol/L) and cancer at sites that have rarely been evaluated. We placed special emphasis on the potential confounding effect of antioxidant vitamins.. Plasma concentrations of cholesterol and antioxidant vitamins were measured in 1971-1973 in 2974 men working in Basel, Switzerland. In 1990, the vital status of all participants was assessed.. Two hundred ninety of the participants had died from cancer, 87 from lung, 30 from prostate, 28 from stomach, and 22 from colon cancer. Group means for plasma cholesterol concentrations did not differ significantly between survivors and those who died from cancer at any of the studied sites. With plasma cholesterol, vitamins C and E, retinol, carotene, smoking, and age accounted for in a Cox model, an increase in total cancer mortality in lung, prostate, and colon but not in stomach cancer mortality was observed in men >60 y of age with low plasma cholesterol. When data from the first 2 y of follow-up were excluded from the analysis, the relative risk estimates remained practically unchanged with regard to lung cancer but decreased for colon, prostate, and overall cancer.. Increased cancer mortality risks associated with low plasma cholesterol were not explained by the confounding effect of antioxidant vitamins, but were attributed in part to the effect of preexisting cancer.

Topics: Age Factors; Ascorbic Acid; Cholesterol; Cohort Studies; Colonic Neoplasms; Follow-Up Studies; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasms; Prospective Studies; Prostatic Neoplasms; Risk Factors; Smoking; Stomach Neoplasms; Switzerland; Vitamin A; Vitamin E

Nitrate and trihalomethanes (THMs) in drinking water are widespread and are potential human carcinogens.. We evaluated the association between drinking-water exposure to nitrate and THMs and prostate cancer.. During the period 2008-2013, 697 hospital-based incident prostate cancer cases (97 aggressive tumors) and 927 population-based controls were recruited in Spain, providing information on residential histories and type of water consumed. Average nitrate and THMs levels in drinking water were linked with lifetime water consumption to calculate waterborne ingestion. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using mixed models with recruitment area as random effect. Effect modification by tumor grade (Gleason score), age, education, lifestyle, and dietary factors was explored.. Findings suggest long-term waterborne ingested nitrate could be a risk factor of prostate cancer, particularly for aggressive tumors. High intakes of fiber, fruit/vegetables and vitamin C may lower this risk. Association with residential levels but not ingested chloroform/Br-THM may suggest inhalation and dermal routes could be relevant for prostate cancer. https://doi.org/10.1289/EHP11391.

Topics: Adult; Ascorbic Acid; Chloroform; Drinking Water; Environmental Exposure; Humans; Male; Nitrates; Prostatic Neoplasms; Spain; Trihalomethanes; Water Pollutants, Chemical

Since prostate cancer is the most commonly diagnosed malignancy in men, the theranostic approach has become very attractive since the discovery of urea-based PSMA inhibitors. Different molecules have been synthesized starting from the Glu-urea-Lys scaffold as the pharmacophore and then optimizing the linker and the chelate to improve functional characteristics. This article aimed to highlight the quality aspects, which could have an impact on clinical practice, describing the development of an Investigational Medicinal Product Dossier (IMPD) for clinical trials with [177Lu]Lu-PSMA-I&T in prostate cancer and other solid tumors expressing PSMA. The results highlighted some important quality issues of the final preparation: radiolabeling of PSMA-I&T with lutetium-177 needs a considerably longer time compared with the radiolabeling of the well-known [177Lu]Lu-PSMA-617. When the final product was formulated in saline, the stability of [177Lu]Lu-PSMA-I&T was reduced by radiolysis, showing a decrease in radiochemical purity (<95% in 24 h). Different formulations of the final product with increasing concentrations of ascorbic acid have been tested to counteract radiolysis and extend stability. A solution of 20 mg/mL of ascorbic acid in saline prevents radiolysis and ensures stability over 30 h.

Topics: Antigens, Surface; Ascorbic Acid; Dipeptides; Glutamate Carboxypeptidase II; Heterocyclic Compounds, 1-Ring; Humans; Male; Prostate-Specific Antigen; Prostatic Neoplasms; Quality Control; Radiopharmaceuticals; Urea

DNA 5-hydroxymethylcytosine (5hmC) is produced by dynamic 5mC oxidation process contributing to tissue specification, and loss of 5hmC has been reported in multiple cancers including genitourinary cancers. However, 5hmC is also cell-type specific, and its variability may exist between differentiated tumor cells and cancer stem cells. Thus, cancer-associated changes in 5hmC may be contributed by distinct sets of tumor cells within the tumor tissues.. Here, we applied a sensitive immunoprecipitation-based method (hMeDIP-seq) to analyze 5hmC changes during genitourinary carcinogenesis (including prostate, urothelial and kidney). We confirmed the tissue-specific distribution of 5hmC in genitourinary tissues and identified regional gain and global loss of 5hmC coexisting in genitourinary cancers. The genes with gain of 5hmC during tumorigenesis were functionally enriched in regulating stemness and hypoxia, whereas were associated with poor clinical prognosis irrespective of their differences in tumor type. We identified that gain of 5hmC occurred in soft fibrin gel-induced 3D tumor spheres with a tumor-repopulating phenotype in two prostate cancer cell lines, 22RV1 and PC3, compared with conventional two-dimensional (2D) rigid dishes. Then, we defined a malignant signature derived from the differentially hydroxymethylated regions affected genes of cancer stem-like cells, which could predict a worse clinical outcome and identified phenotypically malignant populations of cells from prostate cancer tumors. Notably, an oxidation-resistant vitamin C derivative, ascorbyl phosphate magnesium, restored 5hmC and killed the cancer stem cell-like cells leading to apoptosis in prostate cancer cell lines.. Collectively, our study dissects the regional gain of 5hmC in maintaining cancer stem-like cells and related to poor prognosis, which provides proof of concept for an epigenetic differentiation therapy with vitamin C by 5hmC reprogramming.

Topics: 5-Methylcytosine; Ascorbic Acid; Carcinogenesis; DNA; DNA Methylation; Fibrin; Humans; Magnesium; Male; Phosphates; Prostatic Neoplasms; Urogenital Neoplasms

To assess the effect of sequential treatment with Vitamin C (VC) and Quercetin (Q) on Nrf2-related oxidative stress in PC3 and DU145 cells, viability was measured by MTT assay. Intracellular ROS levels were determined, using 2'-7'-dichlorodihydrofluorescein diacetate fluorescent as a probe. Nrf2 gene expression was investigated by quantitative reverse transcription polymerase chain reaction, and Nrf2 protein levels were defined by western blot analysis. The activity of glutathione peroxidase (GPx), glutathione reductase (GR), nicotinamide adenine dinucleotide phosphate dehydrogenase quinone 1 (NQO1) and hemeoxygenase 1 (HO-1) enzymes were measured. The IC

Topics: Ascorbic Acid; Chemoprevention; Humans; Male; NF-E2-Related Factor 2; Oxidative Stress; Prostatic Neoplasms; Quercetin; Reactive Oxygen Species

We aimed first to evaluate the early oxidative stress following radionuclide therapy (RNT) with 177Lu-PSMA and 177Lu-DOTATATE and second to evaluate the protective effect of vitamin C on oxidative stress.. Prostate cancer and neuroendocrine tumor (NET) patients referred to therapy with 177Lu-PSMA and 177Lu-DOTATATE, respectively, were enrolled in this study. The patients divided into the control group underwent routine RNT without any intervention and the intervention group was asked to take effervescent tablets (500 mg) of vitamin C for two days prior to the RNT (three tablets per day). To measure oxidative stress, blood samples were taken immediately before treatment and 48 h after treatment, and the serums were separated and frozen. To evaluate oxidative stress, the serum levels of malondialdehyde (MDA) and glutathione (GSH) and the activity of glutathione reductase were measured before and two days after treatment.. In total, 61 RNT cycles were evaluated in 34 patients with age of 65 ± 2.83 (median ± SE) years (range of 27-99); this total included 20 (59%) prostate cancer patients [35 cycles (57.4%)] and 14 patients (41%) with NET [26 cycles (42.6%)]. Of the 61 evaluated cycles, 27 cycles were given in the control group and 34 cycles were given in the intervention group. The serum level of MDA was significantly increased after treatment compared to before treatment (P = 0.02) in the control group, while no significant change in the serum level of MDA was observed in the intervention group (P = 0.52). The serum level of GSH was insignificantly decreased after treatment compared to before treatment in the control group and slightly increased after treatment in the intervention group (P > 0.05). The serum level of glutathione reductase was insignificantly increased in all groups of patients after treatment (P > 0.05).. According to the results of this study, RNT with Lu-PSMA and Lu-DOTATATE may induce oxidative stress via the generation of free radicals and reactive oxygen species. Consumption of vitamin C prior to RNT may ameliorate this oxidative stress. These preliminary results have positive implications for clinical practice. Verification of these noteworthy results is needed and can be conducted with larger randomized controlled trials with longer time points.

Topics: Adult; Aged; Aged, 80 and over; Ascorbic Acid; Coordination Complexes; Female; Humans; Male; Middle Aged; Neuroendocrine Tumors; Octreotide; Organometallic Compounds; Oxidative Stress; Prostatic Neoplasms; Radiation-Protective Agents

The aim of this study is to investigate the effect of two abundant dietary supplements, quercetin and vitamin C on some factors involved in metastasis and proliferation of prostate cancer, which are resistant to conventional chemotherapies in late stages.. Bone and brain are two common sites of metastases in prostate cancer, nevertheless the factors involved in their metastatic pathways are not well understood.. The effect of quercetin (75µM) and vitamin C (100 µM) on CXCR4, CXCR7 chemokine receptors, α4, α5 and β1 integrins, ki-67 proliferation marker and Vascular endothelial growth factor, VEGF was evaluated using Quantitative Reverse Transcription PCR (RT-qPCR).. The effect of quercetin and vitamin C alone was different on PC3 and DU145 prostate cancer cell lines, but sequential combination reduced significantly the expression of CXCR and CXCR7 chemokine receptors, α4, α5 and β1 integrin subunits, VEGF and Ki-67 proliferation markers in PC3 and DU145 cell lines.. Our results indicated the beneficial effect of quercetin and vitamin C on prostate cancer cells with different metastatic sites and their differential response to the treatment which in turn may lead us to reach suitable therapeutic outcomes to combat cancer (Fig. 3, Ref. 36).

Topics: Ascorbic Acid; Cell Line, Tumor; Fibronectins; Humans; Integrins; Male; Prostatic Neoplasms; Quercetin; Vascular Endothelial Growth Factor A

Traditional treatment regimens for advanced prostate cancer, especially castration-resistant prostate cancer, result in low survival times with severe side effects. Therefore, new treatment options are required. Vitamin C (VC) has been identified as a promising anti-cancer agent of which the effects depend on the accumulation of H. The anti-cancer effect of VC and/or SAS on prostate cancer cells was assessed using WST-8, colony formation and annexin V-FITC/PI FACS assays. Changes in cellular ROS and GSH levels were determined to verify our hypothesis. Finally, BALB/c nude mice bearing prostate cancer xenografts were used to assess the anti-cancer effects of single or combined VC and SAS therapies.. We found that SAS could potentiate the short- and long-term cytotoxicity of VC in prostate cancer cells. We also found that the synergistic effect of SAS and VC led to significant cellular GSH depletion, resulting in increased ROS accumulation. This synergistic effect could be reversed by the antioxidant N-acetyl-L-cysteine (NAC). The synergistic effect of SAS and VC was also noted in prostate cancer xenografts and correlated with immunohistochemistry results.. Our results strongly indicate that SAS, a relatively non-toxic drug that targets cystine transporters, in combination with VC may be superior to their single applications in the treatment of prostate cancer.

Topics: Acetylcysteine; Amino Acid Transport System y+; Animals; Antineoplastic Combined Chemotherapy Protocols; Antioxidants; Apoptosis; Ascorbic Acid; Cell Line, Tumor; Cell Proliferation; Cell Survival; Drug Synergism; Glutathione; Humans; Immunohistochemistry; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Prostatic Neoplasms; Reactive Oxygen Species; Sulfasalazine; Transplantation, Heterologous

Constant development of chemotherapeutic strategies has considerably improved the efficiency of tumor treatment. However, adverse effects of chemotherapeutics enforce premature treatment cessation, which leads to the tumor recurrence and accelerated death of oncologic patients. Recently, sodium ascorbate (ASC) has been suggested as a promising drug for the adjunctive chemotherapy of glioblastoma multiforme (GBM) and prostate cancer (PC). To estimate whether ASC can interfere with tumor recurrence between the first and second-line chemotherapy, we analyzed the effect of high ASC doses on the expansion of cells in vitro and in vivo.. Brightfield microscopy-assisted approaches were used to estimate the effect of ASC (1-14 mM) on the morphology and invasiveness of human GBM, rat PC and normal mouse 3T3 cells, whereas cytostatic/pro-apoptotic activity of ASC was estimated with flow cytometry. These assays were complemented by the in vitro CellROX-assisted analyses of intracellular oxidative stress and in vivo estimation of GBM tumor invasion.. ASC considerably decreased the proliferation and motility of GBM and PC cells. This effect was accompanied by intracellular ROS over-production and necrotic death of tumor cells, apparently resulting from their "autoschizis". In vivo studies demonstrated the retardation of GBM tumor growth and invasion in the rats undergone intravenous ASC administration, in the absence of detectable systemic adverse effects of ASC.. Our data support previous notions on anti-tumor activity of high ASC doses. However, autoschizis-related cell responses to ASC indicate that its application in human adjunctive tumor therapy should be considered with caution.

Topics: Animals; Ascorbic Acid; Brain Neoplasms; Cell Line, Tumor; Cell Proliferation; Dose-Response Relationship, Drug; Glioblastoma; Humans; Male; Mice; Neoplasm Invasiveness; Prostatic Neoplasms; Rats; Reactive Oxygen Species

Prostate-specific antigen (PSA), a serine protease, is a biomarker for preoperative diagnosis and screening of prostate cancer and monitoring of its posttreatment.. In this work, we reported a colorimetric method for clinical detection of PSA using gold nanoparticles (AuNPs) as the reporters. The method is based on ascorbic acid (AA)-induced in situ formation of AuNPs and Cu. The linear range for PSA detection was found to be 0~0.8 ng/mL with a detection limit of 0.02 ng/mL. Because of the separation of cleavage step and measurement step, the interference of matrix components in biological samples was avoided.. The high extinction coefficient of AuNPs facilitates the colorimetric analysis of PSA in serum samples. This work is helpful for designing of other protease biosensors by matching specific peptide substrates.

Topics: Ascorbic Acid; Biosensing Techniques; Colorimetry; Copper; Gold; Humans; Immobilized Proteins; Limit of Detection; Male; Metal Nanoparticles; Prostate-Specific Antigen; Prostatic Neoplasms

Topics: Antineoplastic Agents; Ascorbic Acid; Glucosephosphate Dehydrogenase Deficiency; Hematologic Diseases; Humans; Male; Middle Aged; Oxidative Stress; Prostatic Neoplasms; Renal Insufficiency

Cancer cells typically experience higher oxidative stress than normal cells, such that elevating pro-oxidant levels can trigger cancer cell death. Although pre-exposure to mild oxidative agents will sensitize cancer cells to radiation, this pre-exposure may also activate the adaptive stress defense system in normal cells. Ascorbic acid is a prototype redox modulator that when infused intravenously appears to kill cancers without injury to normal tissues; however, the mechanisms involved remain elusive. In this study, we show how ascorbic acid kills cancer cells and sensitizes prostate cancer to radiation therapy while also conferring protection upon normal prostate epithelial cells against radiation-induced injury. We found that the NF-κB transcription factor RelB is a pivotal determinant in the differential radiosensitization effects of ascorbic acid in prostate cancer cells and normal prostate epithelial cells. Mechanistically, high reactive oxygen species concentrations suppress RelB in cancer cells. RelB suppression decreases expression of the sirtuin SIRT3 and the powerful antioxidant MnSOD, which in turn increases oxidative and metabolic stresses in prostate cancer cells. In contrast, ascorbic acid enhances RelB expression in normal cells, improving antioxidant and metabolic defenses against radiation injury. In addition to showing how RelB mediates the differential effects of ascorbic acid on cancer and normal tissue radiosensitivities, our work also provides a proof of concept for the existence of redox modulators that can improve the efficacy of radiotherapy while protecting against normal tissue injury in cancer settings.

Topics: Animals; Antioxidants; Apoptosis; Ascorbic Acid; Cell Proliferation; Cells, Cultured; Humans; Male; Mice; Mice, Nude; Oxidative Stress; Prostate; Prostatic Neoplasms; Radiation Tolerance; Radiation-Sensitizing Agents; Radiation, Ionizing; Reactive Oxygen Species; Superoxide Dismutase; Transcription Factor RelB; Xenograft Model Antitumor Assays

The purpose of this study was to determine the relationship between total antioxidant capacity (TAC) from diet and supplements and prostate cancer aggressiveness among 855 African Americans (AA) and 945 European Americans (EA) in the North Carolina-Louisiana Prostate Cancer Project (PCaP). Cases were classified as either high aggressive, low aggressive, or intermediate aggressive. TAC was calculated from the vitamin C equivalent antioxidant capacity of 42 antioxidants measured via food frequency questionnaire. EA reported greater dietary TAC from diet and supplements combined (P < 0.0001). In both minimally and fully adjusted logistic regression models, TAC from diet and supplements combined was associated with a reduced odds of high aggressive prostate cancer in all men, AA and EA: odds ratios for highest vs. lowest level (>1500 vs. <500 mg vitamin C equivalent/day): 0.31 [95% confidence interval (CI): 0.15, 0.67; P-trend < 0.01], 0.28 (95% CI: 0.08, 0.96; P-trend < 0.001), and 0.36 (95% CI: 0.15, 0.86; P-trend = 0.58), respectively. These associations did not appear to differ between AA and EA. These data suggest that greater intake of antioxidants is associated with less aggressive prostate cancer. Additional research is needed to confirm these results and determine the underlying mechanisms.

Topics: Adult; Aged; Antioxidants; Ascorbic Acid; Black or African American; Dietary Supplements; Feeding Behavior; Humans; Logistic Models; Louisiana; Male; Middle Aged; North Carolina; Prostatic Neoplasms; Socioeconomic Factors; White People

Scanning (SEM) and transmission electron microscopy (TEM) were used to characterize the cytotoxic effects of ascorbate (VC), menadione (VK3), or a VC:VK3 combination on a human prostate carcinoma cell line (DU145) following a 1-h vitamin treatment and a subsequent 24-h incubation in culture medium. Cell alterations examined by light and electron microscopy were treatment-dependent with VC + VK3 >VK3 > VC > Sham. Oxidative stress-induced damage was found in most organelles. This report describes injuries in the tumor cell nucleus (chromatin and nucleolus), mitochondria, endomembranes, lysosomal bodies (autophagocytoses) and inclusions. Morphologic alterations suggest that cytoskeleton damage is likely responsible for the superficial cytoplasmic changes, including major changes in cell shape and size and the self-excising phenomena. Unlike apoptotic bodies, the excised pieces contain ribonucleoproteins, but not organelles. These deleterious events cause a progressive, significant reduction in the tumor cell size. During nuclear alterations, the nuclei maintain their envelope during chromatolysis and karyolysis until cell death, while nucleoli undergo a characteristic segregation of their components. In addition, changes in fat and glycogen storage are consistent the cytotoxic and metabolic alterations caused by the respective treatments. All cellular ultrastructural changes are consistent with cell death by autoschizis and not apoptosis or other kinds of cell death.

Topics: Adenocarcinoma; Ascorbic Acid; Cell Death; Cell Line, Tumor; Cell Nucleus; Cytoskeleton; Humans; Male; Microscopy, Electron; Organelles; Prostatic Neoplasms; Vitamin K 3

This study explores the link between the antiproliferative activity of emodin through the generation of reactive oxygen species (ROS) in various cancer cell lines and the expression of the androgen receptor (AR) in the prostate cancer cell lines LNCaP (androgen-sensitive) and PC-3 (androgen-refractory), as well as the pro-metastatic low-density lipoprotein receptor-related protein 1 (LRP1) in the above prostate cancer cells and the nonprostate cell lines A549 (lung), HCT-15 (colon) and MG-63 (bone) under normoxic and hypoxia-like conditions. Among all cell lines, emodin showed most growth inhibition in LNCaP, followed by A549. The mechanism of cytotoxicity of emodin was postulated to be the widely reported ROS generation, based on the observations of poor in vitro radical-scavenging activity and increased growth inhibition of emodin by ascorbic acid (AA) pre-treatment owing to the additive effects of ROS generation by emodin and pro-oxidant effects of AA. Emodin downregulated AR in LNCaP under normoxic and hypoxia-like conditions (simulated by CoCl(2)) and LRP1 under normoxia. Emodin upregulated LRP1 in other cell lines, except HCT-15, under normoxic, and even more markedly under hypoxia-like conditions. The downregulation of AR in LNCaP and upregulation of LRP1 in all cell lines, except HCT-15, under hypoxia-like conditions along with growth inhibition by emodin, suggests that emodin may be a useful therapeutic option against androgen-sensitive prostate cancer and other such LRP1-expressing cancers to attempt the targeting of the elevated LRP1 levels to allow the uptake of emodin and/or any other accompanying therapeutic agents by LRP1.

Topics: Ascorbic Acid; Cell Line, Tumor; Down-Regulation; Emodin; Gene Expression Regulation, Neoplastic; Humans; Hypoxia; Low Density Lipoprotein Receptor-Related Protein-1; Male; Prostatic Neoplasms; Reactive Oxygen Species; Receptors, Androgen; Up-Regulation

Immunotherapy has become an attractive new strategy in the treatment of cancer. The laboratory and clinical study of cancer immunotherapy is rapidly advancing. However, in the clinical setting, the results of cancer immunotherapy are mixed. We therefore contend that cancer immunotherapy should be customized to each patient individually based on their immune status and propose an integrative immunotherapy approach with second-generation group-specific component macrophage activating factor (GcMAF)-containing human serum.. The standard protocol of our integrative cancer immunotherapy is as follows: i) 0.5 ml GcMAF-containing human serum is administered intramuscularly or subcutaneously once or twice per week for the duration of cancer therapy until all cancer cells are eradicated; ii) hyper T/natural killer (NK) cell therapy is given once per week for six weeks; iii) high-dose vitamin C is administered intravenously twice per week; iv) alpha lipoic acid (600 mg) is administered orally daily; v) vitamin D3 (5,000-10,000 IU) is administered orally daily.. By March 2013, Saisei Mirai have treated over 345 patients with GcMAF. Among them we here present the cases of three patients for whom our integrative immunotherapy was remarkably effective.. The results of our integrative immunotherapy seem hopeful. We also plan to conduct a comparative clinical study.>

Topics: Aged; Ascorbic Acid; Bone Neoplasms; Cell- and Tissue-Based Therapy; Combined Modality Therapy; Female; Humans; Immunotherapy; Injections, Intramuscular; Injections, Subcutaneous; Liver Neoplasms; Lung Neoplasms; Macrophage-Activating Factors; Male; Prognosis; Prostatic Neoplasms; Thioctic Acid; Thymus Neoplasms; Vitamin D-Binding Protein

Ascorbic acid (AA) is capable of inhibiting cancer cell growth by perturbing the normal redox state of cells and causing toxic effects through the generation of abundant reactive-oxygen species (ROS). However, the clinical utility of AA at a tolerable dosage is plagued by a relatively low in vivo efficacy. This study describes the development of a peroxidase-like composite nanoparticle for use in an AA-mediated therapeutic strategy. On the basis of a high-throughput, one-pot solvothermal approach, Fe3O4@C nanoparticles (NPs) were synthesized and then modified with folic acid (FA) on the surface. Particular focus is concentrated on the assessment of peroxidase-like catalytic activity by a chromogenic reaction in the presence of H2O2. The carbon shell of Fe3O4@C NPs contains partially graphitized carbon and thus facilitates electron transfer in the catalytic decomposition of H2O2, leading to the production of highly reactive hydroxyl radicals. Along with magnetic responsiveness and receptor-binding specificity, the intrinsic peroxidase-like catalytic activity of Fe3O4@C-FA NPs pronouncedly promotes AA-induced oxidative stress in cancer cells and optimizes the ROS-mediated antineoplastic efficacy of exogenous AA. In vitro experiments using human prostate cancer PC-3 cells demonstrate that Fe3O4@C-FA NPs serve as a peroxidase mimic to create hydroxyl radicals from endogenous H2O2 that is yielded in response to exogenous AA via an oxidative stress process. The usage of a dual agent leads to the enhanced cytotoxicity of PC-3 cells, and, because of the synergistic effect of NPs, the administrated dosage of AA is reduced markedly. However, because normal cells (HEK 293T cells) appear to have a higher capacity to cope with additionally generated ROS than cancer cells, the NP-AA combination shows little damage in this case, proving that selective killing of cancer cells could be achieved owing to preferential accumulation of ROS in cancer cells. A possible ROS-mediated mechanism is discussed to elucidate the pharmaceutical profile of the NP-AA agent. In general, this foundational study reveals that the peroxidase-like nanomaterials are applicable for modulating oxidative stress for the selective treatment of cancer cells by generating a high level of endogenous ROS.

Topics: Ascorbic Acid; Carbon; Cell Line, Tumor; Ferric Compounds; Humans; Male; Nanoparticles; Oxidative Stress; Peroxidase; Prostatic Neoplasms

Recent studies have revealed the scientific basis for the use of intravenous (i.v.) vitamin C or ascorbic acid (ascorbate) in treating cancers, and raised the possibility of using i.v. ascorbate as a prooxidant anticancer therapy. Through the production of H2O2, pharmacologic ascorbate can induce some cancer cell death in vitro and inhibit a number of types of tumor growth in animal models. However, the mechanism of cell death triggered by ascorbate is not well understood. In this study, we investigated the cytotoxicity of pharmacological concentrations of ascorbate to human prostate cancer cells and the mechanisms involved. The results showed that ascorbate in the millimolar range induced cytotoxicity in five of the six tested prostate cancer cell lines. The IC50 values in the sensitive prostate cancer cells ranged from 1.9 to 3.5 mmol/l, concentrations clinically achievable with i.v. ascorbate use. All tested androgen-independent cells were sensitive to ascorbate treatment. The ascorbate-insensitive cell line LaPC4 is hormonally dependent. Whereas the reasons for sensitivity/resistance to ascorbate treatment need to be investigated further, cell death in sensitive cells was dependent on H2O2. Ascorbate treatment depleted ATP and induced autophagy in sensitive prostate cancer cells, resulting in cell death. Taken together with previous studies, high-dose ascorbate has the potential to be a novel treatment option to hormone-refractory prostate cancer.

Topics: Adenosine Triphosphate; Antineoplastic Agents; Apoptosis; Ascorbic Acid; Autophagy; Cell Line, Tumor; Chromatography, High Pressure Liquid; Drug Screening Assays, Antitumor; Humans; Hydrogen Peroxide; Male; Neoplasms, Hormone-Dependent; Prostatic Neoplasms

Cellular reactive oxygen species (ROS) production is increased by both temperature and anticancer drugs. Antioxidants are known to suppress ROS production while cancer patients may take them as dietary supplement during chemotherapy and hyperthermic therapy. We examined changes in ROS production in prostate cancer cells in the presence of various anticancer drugs and antioxidants at different temperatures. ROS production was increased with temperature in cancer cells, but not in normal cells; this increase was potently inhibited by ascorbic acid. ROS production was also increased in the presence of some anticancer drugs, such as vinblastine, but not by others. Dietary antioxidant supplements, such as β-carotene, showed variable effects. Ascorbic acid potently inhibited ROS production, even in the presence of anticancer drugs, while β-carotene showed no inhibition. Accordingly, our results suggest that cancer patients should carefully choose antioxidants during their cancer chemotherapy and/or hyperthermic therapy.

Topics: Animals; Antineoplastic Agents; Antioxidants; Ascorbic Acid; Dextrans; Hyperthermia, Induced; Magnetite Nanoparticles; Male; Prostatic Neoplasms; Rats; Reactive Oxygen Species; Tumor Cells, Cultured

Induction of osteoblast differentiation by paracrine Sonic hedgehog (Shh) signaling may be a mechanism through which Shh-expressing prostate cancer cells initiate changes in the bone microenvironment and promote metastases. A hallmark of osteoblast differentiation is the formation of matrix whose predominant protein is type 1 collagen. We investigated the formation of a collagen matrix by osteoblasts cultured with prostate cancer cells, and its effects on interactions between prostate cancer cells and osteoblasts.. In the presence of exogenous ascorbic acid (AA), a co-factor in collagen synthesis, mouse MC3T3 pre-osteoblasts in mixed cultures with human LNCaP prostate cancer cells or LNCaP cells modified to overexpress Shh (LNShh cells) formed collagen matrix with distinct fibril ultrastructural characteristics. AA increased the activity of alkaline phosphatase and the expression of the alkaline phosphatase gene Akp2, markers of osteoblast differentiation, in MC3T3 pre-osteoblasts cultured with LNCaP or LNShh cells. However, the AA-stimulated increase in Akp2 expression in MC3T3 pre-osteoblasts cultured with LNShh cells far exceeded the levels observed in MC3T3 cells cultured with either LNCaP cells with AA or LNShh cells without AA. Therefore, AA and Shh exert a synergistic effect on osteoblast differentiation. We determined whether the effect of AA on LNShh cell-induced osteoblast differentiation was mediated by Shh signaling. AA increased the expression of Gli1 and Ptc1, target genes of the Shh pathway, in MC3T3 pre-osteoblasts cultured with LNShh cells to at least twice their levels without AA. The ability of AA to upregulate Shh signaling and enhance alkaline phosphatase activity was blocked in MC3T3 cells that expressed a dominant negative form of the transcription factor GLI1. The AA-stimulated increase in Shh signaling and Shh-induced osteoblast differentiation was also inhibited by the specific collagen synthesis inhibitor 3,4-dehydro-L-proline.. Matrix collagen, formed by osteoblasts in the presence of AA, potentiates Shh signaling between Shh-expressing prostate cancer cells and osteoblasts. Collagen and Shh signaling exert a synergistic effect on osteoblast differentiation, a defining event in prostate carcinoma bone metastasis. Investigations into paracrine interactions among prostate cancer cells, osteoblasts, and osteoblast-synthesized matrix proteins advance our understanding of mechanisms contributing to prostate cancer bone metastasis.

Topics: Alkaline Phosphatase; Animals; Ascorbic Acid; Cell Differentiation; Cell Line, Tumor; Coculture Techniques; Fibrillar Collagens; Hedgehog Proteins; Histocytochemistry; Humans; Male; Mice; Osteoblasts; Paracrine Communication; Particle Size; Prostatic Neoplasms; Up-Regulation

The redox-silent vitamin E analog α-tocopheryl succinate (α-TOS) was found to synergistically cooperate with vitamin K3 (VK3) plus ascorbic acid (AA) in the induction of cancer cell-selective apoptosis via a caspase-independent pathway. Here we investigated the molecular mechanism(s) underlying cell death induced in prostate cancer cells by α-TOS, VK3 and AA, and the potential use of targeted drug combination in the treatment of prostate cancer.. The generation of ROS, cellular response to oxidative stress, and autophagy were investigated in PC3 prostate cancer cells by using drugs at sub-toxic doses. We evaluated whether PARP1-mediated apoptosis-inducing factor (AIF) release plays a role in apoptosis induced by the combination of the agents. Next, the effect of the combination of α-TOS, VK3 and AA on tumor growth was examined in nude mice. VK3 plus AA induced early ROS formation associated with induction of autophagy in response to oxidative stress, which was reduced by α-TOS, preventing the formation of autophagosomes. α-TOS induced mitochondrial destabilization leading to the release of AIF. Translocation of AIF from mitochondria to the nucleus, a result of the combinatorial treatment, was mediated by PARP1 activation. The inhibition of AIF as well as of PARP1 efficiently attenuated apoptosis triggered by the drug combination. Using a mouse model of prostate cancer, the combination of α-TOS, VK3 and AA was more efficient in tumor suppression than when the drugs were given separately, without deleterious side effects.. α-TOS, a mitochondria-targeting apoptotic agent, switches at sub-apoptotic doses from autophagy-dependent survival of cancer cells to their demise by promoting the induction of apoptosis. Given the grim prognosis for cancer patients, this finding is of potential clinical relevance.

Topics: Animals; Apoptosis Inducing Factor; Ascorbic Acid; Autophagy; Caspases; Cell Line, Tumor; Disease Progression; Humans; Male; Mice; Poly(ADP-ribose) Polymerases; Prostatic Neoplasms; Protein Transport; Reactive Oxygen Species; Succinates; Vitamin K 3; Xenograft Model Antitumor Assays

While the benefits of ascorbic acid (vitamin C, ascorbate) as an essential nutrient are well established, its effects on tumor cells and in tumor treatment are controversial. In particular, conflicting data exist whether ascorbate may increase the cytotoxic effects of antineoplastic drugs or may rather exert adverse effects on drug sensitivity during cancer treatment. Findings are further obscured regarding the distinction between ascorbate and dehydroascorbate (DHA). Thus, the purpose of this study was to evaluate and directly compare the cytotoxic efficacy of ascorbate compared to DHA, and to analyse if ascorbate at pharmacological concentrations affects the efficacy of antineoplastic agents in prostate carcinoma cells.. We directly compare the effects of ascorbate (supplied as 'Pascorbin solution for injection') and DHA on tumor cell viability, and determine IC(50) values for various cell lines. At concentrations well below the IC(50), ascorbate effects on cell proliferation and cell cycle are analysed. We furthermore determine changes in cellular sensitivity towards various cytostatic drugs upon pre-treatment of cells with ascorbate.. We demonstrate higher therapeutic efficacy of ascorbate over DHA in various cell lines, independent of cell line-specific differences in ascorbate sensitivity, and identify the extracellular generation of H(2)O(2) as critical mechanism of ascorbate action. We furthermore show that, in addition to pro-apoptotic effects described previously, ascorbate treatment already at concentrations well below the IC(50) exerts anti-proliferative effects on tumor cells. Those are based on interference with the cell cycle, namely by inducing a G(0)/G(1) arrest. Pre-treatment of tumor cells with ascorbate leads to increased cellular sensitivity towards Docetaxel, Epirubicin, Irinotecan and 5-FU, but not towards Oxaliplatin and Vinorelbin. For Docetaxel and 5-FU, a linear correlation between this sensitizing effect and the ascorbate dosage is observed.. The redox-active form of vitamin C, ascorbate, shows therapeutic efficacy in tumor cells. These antitumor effects of ascorbate are mainly based on its extracellular action and, in addition to the induction of apoptosis, also include an anti-proliferative effect by inducing cell cycle arrest. Furthermore, ascorbate treatment specifically enhances the cytostatic potency of certain chemotherapeutics, which implicates therapeutic benefit during tumor treatment.

Topics: Antineoplastic Agents; Apoptosis; Ascorbic Acid; Camptothecin; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Cell Survival; Dehydroascorbic Acid; Docetaxel; Drug Synergism; Epirubicin; Humans; Irinotecan; Male; Organoplatinum Compounds; Oxaliplatin; Prostatic Neoplasms; Taxoids; Vinblastine; Vinorelbine

To investigate whether clinically relevant levels of epigallocatechin gallate (EGCG, a component of green tea) or vitamin C (ascorbic acid) could antagonize bortezomib antitumor activity in CWR22 human prostate xenograft tumors.. The pharmacokinetics (PK) of EGCG and ascorbic acid were determined in immunocompromised mice and compared with concentrations measured in human PK studies of dietary supplements. Antitumor activity of bortezomib in combination with EGCG or ascorbic acid was determined using several dosing regimens to evaluate different target plasma concentrations of EGCG and ascorbic acid.. Bortezomib dosed twice-weekly at 0.8 mg/kg IV demonstrated tumor growth inhibition (TGI) of 53.9-58.9%. However, when combined with EGCG such that the plasma concentrations of EGCG were >200 μM at the time of bortezomib dosing, all antitumor activity was abrogated (TGI = -17.7%). A lower concentration of EGCG (11-16 μM), which is severalfold higher than measured clinically in humans taking EGCG supplements (0.6-3 μM), was not antagonistic to bortezomib (TGI 63.5%). Pharmacodynamic studies of proteasome inhibition reflected these findings. Ascorbic acid (40 and 500 mg/kg PO daily) was evaluated under a similar study design and did not antagonize bortezomib antitumor activity (TGI 57.2 and 72.2%).. No antagonism of bortezomib is seen in preclinical in vivo experiments, where EGCG or ascorbic acid plasma concentrations are commensurate with dietary or supplemental intake. The data suggest that patients receiving bortezomib treatment do not need to avoid normal dietary consumption of green tea, vitamin C-containing foods, or EGCG or vitamin C dietary supplements.

Topics: Animals; Antineoplastic Agents; Ascorbic Acid; Boronic Acids; Bortezomib; Catechin; Chromatography, Liquid; Drug Screening Assays, Antitumor; Female; Humans; Male; Mice; Mice, SCID; Prostatic Neoplasms; Pyrazines; Tandem Mass Spectrometry; Tea; Xenograft Model Antitumor Assays

Over the last decade, epidemiological, experimental and clinical studies have implicated oxidative stress in the development and progression of prostate cancer. In the present study, we evaluated the oxidative status and antioxidant defense in patients with prostate cancer (PCa) taking into consideration: treatment, Gleason score and bone metastasis. For this, we measured concentrations of plasmatic thiobarbituric acid reactive substances (TBARS), serum protein carbonylation, whole blood catalase (CAT) and superoxide dismutase (SOD) activities, as well as the plasma and erythrocyte thiol levels and serum vitamin C and E concentration. This study was performed on 55 patients with PCa and 55 healthy men. TBARS levels and serum protein carbonylation were higher in PCa patients than in controls and altered levels of antioxidants were found in these patients. CAT activity was decreased and SOD activity was higher in PCa patients when compared with controls. Non-protein thiol levels were increased, however, serum vitamin C and vitamin E content were reduced in PCa patients when compared with controls. In addition, different parameters analyzed in PCa patients based on metastasis, treatment and Gleason score showed changes in oxidative stress biomarkers and antioxidant defenses. These findings may indicate an imbalance in the oxidant/antioxidant status, supporting the idea that oxidative stress plays a role in PCa, moreover, the oxidative profile appear to be modified by bone metastasis, treatment and Gleason score.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Ascorbic Acid; Bone Neoplasms; Catalase; Cyproterone Acetate; Erythrocytes; Goserelin; Humans; Lipid Peroxidation; Male; Middle Aged; Neoplasm Grading; Oxidative Stress; Prostatic Neoplasms; Protein Carbonylation; Sulfhydryl Compounds; Superoxide Dismutase; Thiobarbituric Acid Reactive Substances; Vitamin E

A strategy to reduce the secondary effects of anti-cancer agents is to potentiate the therapeutic effect by their combination. A combination of vitamin K3 (VK3) and ascorbic acid (AA) exhibited an anti-cancer synergistic effect, associated with extracellular production of H(2)O(2) that promoted cell death.. The redox-silent vitamin E analogue alpha-tocopheryl succinate (alpha-TOS) was used in combination with VK3 and AA to evaluate their effect on prostate cancer cells.. Prostate cancer cells were sensitive to alpha-TOS and VK3 treatment, but resistant to AA upto 3.2 mM. When combined, a synergistic effect was found for VK3-AA, whereas alpha-TOS-VK3 and alpha-TOS-AA combination showed an antagonist and additive effect, respectively. However, sub-lethal doses of AA-VK3 combination combined with a sub-toxic dose of alpha-TOS showed to induce efficient cell death that resembles autoschizis. Associated with this cell demise, lipid peroxidation, DNA damage, cytoskeleton alteration, lysosomal-mitochondrial perturbation, and release of cytochrome c without caspase activation were observed. Inhibition of lysosomal proteases did not attenuate cell death induced by the combined agents. Furthermore, cell deaths by apoptosis and autoschizis were detected.. These finding support the emerging idea that synergistic combinations of some agents can overcome toxicity and other side-effects associated with high doses of single drugs creating the opportunity for therapeutically relevant selectivity.

Topics: alpha-Tocopherol; Antineoplastic Combined Chemotherapy Protocols; Antioxidants; Ascorbic Acid; Cell Death; Cell Line, Tumor; Drug Screening Assays, Antitumor; Drug Synergism; Fibroblasts; Humans; Lysosomes; Male; Mitochondria; Prostatic Neoplasms; Reactive Oxygen Species; Vitamin K 3

Ascorbic acid (AA) has been reported to inhibit tumor cell growth through the generation of extracellular hydrogen peroxide (H(2)O(2)). However, the clinical utility of AA has been limited by relatively low potency and in vivo efficacy. This study reports that the metalloporphyrin, Mn(III) tetrakis(N-methylpyridinium-2-yl)porphyrin(5+) (MnTMPyP), has a potent synergistic cytotoxic effect when combined with AA in a variety of cancer cell lines. In the presence of MnTMPyP, the concentration of AA required to inhibit cancer cell growth was markedly reduced. In vitro (cell-free) experiments demonstrated that AA alone enhanced the Fenton reaction that produces cytotoxic hydroxyl radical (HO(*)); however, this reaction was limited by the low rate by which AA generates H(2)O(2) (Fenton reaction substrate) from O(2). MnTMPyP catalyzed H(2)O(2) generation through the AA-facilitated Mn(II <--> III)TMPyP redox cycle and thereby markedly potentiated the Fenton reaction. Accordingly, MnTMPyP and AA resulted in increased cellular levels of H(2)O(2) and HO(*) in cancer cells, which mediate the synergistic cytotoxicity of this combined treatment. This effect was inhibited by cellular enzymes that metabolize H(2)O(2), such as catalase and glutathione peroxidase, suggesting that selective killing of cancer cells deficient in such enzymes can be achieved in vivo.

Topics: Antioxidants; Apoptosis; Ascorbic Acid; Blotting, Western; Catalase; Cell Proliferation; Drug Synergism; Glutathione; Glutathione Reductase; Humans; Hydrogen Peroxide; Hydroxyl Radical; Liver Neoplasms; Male; Manganese; Membrane Potential, Mitochondrial; Metalloporphyrins; Neoplasms, Hormone-Dependent; Oxidation-Reduction; Pancreatic Neoplasms; Prostatic Neoplasms; Reactive Oxygen Species; Superoxides; Tumor Cells, Cultured

Current treatment options for advanced and hormone refractory prostate cancer are limited and responses to commonly used androgen pathway inhibitors are often unsatisfactory. Our recent results indicated that sodium ionophore monensin is one of the most potent and cancer-specific inhibitors in a systematic sensitivity testing of most known drugs and drug-like molecules in a panel of prostate cancer cell models. Because monensin has been extensively used in veterinary applications to build muscle mass in cattle, the link to prostate cancer and androgen signaling was particularly interesting. Here, we showed that monensin effects at nanomolar concentrations are linked to induction of apoptosis and potent reduction of androgen receptor mRNA and protein in prostate cancer cells. Monensin also elevated intracellular oxidative stress in prostate cancer cells as evidenced by increased generation of intracellular reactive oxygen species and by induction of a transcriptional profile characteristic of an oxidative stress response. Importantly, the antiproliferative effects of monensin were potentiated by combinatorial treatment with the antiandrogens and antagonized by antioxidant vitamin C. Taken together, our results suggest monensin as a potential well-tolerated, in vivo compatible drug with strong proapoptotic effects in prostate cancer cells, and synergistic effects with antiandrogens. Moreover, our data suggest a general strategy by which the effects of antiandrogens could be enhanced by combinatorial administration with agents that increase oxidative stress in prostate cancer cells.

Topics: Aldehyde Dehydrogenase; Androgen Antagonists; Androgens; Animals; Apoptosis; Ascorbic Acid; Cattle; Cell Line, Tumor; Cell Proliferation; Cell Survival; Cholesterol; Gene Expression Regulation, Neoplastic; Humans; Male; Monensin; Oxidative Stress; Progesterone; Prostatic Neoplasms; Protein Transport; Receptors, Androgen; Signal Transduction; Subcellular Fractions; Terfenadine

The oxidizing anticancer system of vitamin C and vitamin K₃ (VC:VK₃, producing hydrogen peroxide via superoxide) was combined individually with melatonin, curcumin, quercetin, or cholecalciferol (VD₃) to determine interactions. Substrates were LNCaP and PC-3 prostate cancer cell lines. Three of the tested antioxidants displayed differences in cell line cytotoxicity. Melatonin combined with VC:VK₃ quenched the oxidizing effect, while VC:VK₃ applied 24 hours after melatonin showed no quenching. With increasing curcumin concentrations, an apparent combined effect of VC:VK₃ and curcumin occurred in LNCaP cells, but not PC-3 cells. Quercetin alone was cytotoxic on both cell lines, but demonstrated an additional 50-percent cytotoxicity on PC-3 cells when combined with VC:VK₃. VD₃ was effective against both cell lines, with more effect on PC-3. This effect was negated on LNCaP cells with the addition of VC:VK₃. In conclusion, a natural antioxidant can enhance or decrease the cytotoxicity of an oxidizing anticancer system in vitro, but generalizations about antioxidants cannot be made.

Topics: Antineoplastic Agents; Antioxidants; Ascorbic Acid; Cell Cycle; Cholecalciferol; Curcumin; Cytotoxins; Drug Interactions; Drug Therapy, Combination; Humans; Male; Melatonin; Oxidative Stress; Prostatic Neoplasms; Quercetin; Tumor Cells, Cultured; Vitamin K 3

Topics: Antioxidants; Ascorbic Acid; Dietary Supplements; Humans; Male; Neoplasms; Prostatic Neoplasms; Selenium; Vitamin E

Topics: Antioxidants; Ascorbic Acid; beta Carotene; Colorectal Neoplasms; Confounding Factors, Epidemiologic; Dietary Supplements; Female; Folic Acid; Humans; Incidence; Lung Neoplasms; Male; Neoplasms; Primary Prevention; Prostatic Neoplasms; Randomized Controlled Trials as Topic; Risk Assessment; Selenium; United States; Vitamin B 12; Vitamin B 6; Vitamin E

Topics: Antioxidants; Ascorbic Acid; Humans; Male; Prostatic Neoplasms; Selenium; Vitamin E

Topics: Antioxidants; Ascorbic Acid; Humans; Male; Prostatic Neoplasms; Selenium; Vitamin E

Topics: Aged; Ascorbic Acid; Cardiovascular Diseases; Clinical Protocols; Clinical Trials as Topic; Data Interpretation, Statistical; Humans; Male; Middle Aged; Neoplasms; Oxidative Stress; Patient Compliance; Prostatic Neoplasms; Vitamin E

Topics: Aged; Anticarcinogenic Agents; Ascorbic Acid; Clinical Trials, Phase II as Topic; Colorectal Neoplasms; Dietary Supplements; Humans; Incidence; Lung Neoplasms; Male; Middle Aged; Neoplasms; Physicians; Prostatic Neoplasms; Randomized Controlled Trials as Topic; United States; Vitamin E

Topics: alpha-Tocopherol; Antioxidants; Ascorbic Acid; Clinical Trials as Topic; Dietary Supplements; Humans; Male; Prostatic Neoplasms; Selenium

The epidemiologic evidence on dietary vitamins E and C and prostate cancer is controversial. Therefore, a case-control study was carried out to investigate the role of dietary intake of vitamins E and C in the etiology of prostate cancer.. Cases were 1 294 men with incident, histologically confirmed prostate cancer, admitted to the major teaching and general hospitals of five Italian areas between 1991 and 2002. Controls were 1 451 men admitted for acute, non-neoplastic conditions to the same hospitals. Information on dietary habits and nutrient intake was elicited using a validated food frequency questionnaire including 78 food groups and recipes. Odds ratios (OR) and 95% confidence intervals (CI) for increasing levels of vitamin intake were estimated after allowance for total energy intake and other confounding factors.. Vitamin E showed a significant inverse association with prostate cancer (OR = 0.78 for the highest versus the lowest tertile of intake, 95% CI: 0.58-0.96; p-value for trend = 0.02), whereas for vitamin C the inverse association was of borderline statistical significance (OR = 0.86; 95% CI: 0.65-1.08). Results were consistent in strata of age, body mass index, and family history of prostate cancer.. The present study shows an inverse association between dietary intake of vitamins E and prostate cancer incidence. This finding is likely to reflect the influence of diet itself since supplementation or food fortification with vitamins is rare in the Italian population.

Topics: Aged; Antioxidants; Ascorbic Acid; Case-Control Studies; Diet; Humans; Incidence; Italy; Male; Middle Aged; Prostatic Neoplasms; Risk Factors; Vitamin E

Oxidative stress has been implicated in the etiology of several pathologies.. The study was designed to investigate the levels of antioxidants and lipid peroxidation (LPO) in relation to prostate-specific antigen (PSA) levels in blood of Nigerian prostate cancer (PCa) patients.. One hundred twenty PCa patients were assigned to 3 groups; group 1 (low grade) with a PSA level of 5-10 ng/ml (n = 33), group 2 (medium grade) with PSA of 11-20 ng/ml (n = 45) and group 3 (high grade) with PSA >20 ng/ml (n = 42). The control group comprised 50 healthy subjects with PSA <3.0 ng/ml.. Subjects with a PSA level of 11-20 ng/ml and PSA >20 ng/ml had significantly lower uric acid and reduced glutathione levels (p <0.05). A significant reduction (p <0.05) in plasma vitamin C and E levels was observed in these patients. The levels of vitamins C and E decreased by 27% and 77% in subjects with PSA >20 ng/ml, and by 25% and 47% in subjects with a PSA level of 11-20 ng/ml, respectively. Serum total bilirubin, alkaline phosphatase (ALP) and LPO were significantly (p <0.05) elevated in subjects with PSA >11 ng/ml. More specifically, total bilirubin, ALP and LPO levels were elevated by 75%, 66% and 107% in subjects with PSA at 11-20 ng/ml, and by 167%, 105%, 98% in subjects with PSA > or = 20 ng/ml, respectively. Moreover, superoxide dismutase and catalase activities were lower (p <0.05) in all cancer patients.. The results confirmed the depletion of antioxidants in PCa patients, and an inverse relationship between antioxidants and PSA values in this group.

Topics: Adult; Aged; Antioxidants; Ascorbic Acid; Case-Control Studies; Female; Humans; Lipid Peroxidation; Male; Middle Aged; Nigeria; Oxidative Stress; Prostatic Neoplasms; Reference Values; Severity of Illness Index; Vitamin E

Topics: Aged; Area Under Curve; Ascorbic Acid; Drug Administration Schedule; Half-Life; Humans; Male; Prostatic Neoplasms

The anticarcinogenic and antioxidant properties of vitamins A, C, E and pro- or antioxidant properties of trace metals have recently attracted increased attention. We examined the levels of antioxidant vitamins (A, C and E), selenium and malondialdehyde (MDA), and trace metals (Fe, Ni, Zn, Co and Cu) in patients with prostate cancer. In total, 41 subjects (21 controls and 20 prostate cancer patients) were included in the study. The levels of trace elements and Fe in whole blood were determined by atomic absorption spectrophotometry. Serum levels of Se were determined using a fluorimetric method, while a HPLC method was used for serum levels of vitamins and MDA. The levels of vitamins A and E were significantly lower and MDA levels were significantly higher (p<0.001) in patients with prostate cancer compared to controls. Serum vitamin C was significantly lower in patients with prostate cancer when compared to controls (p<0.01). Moreover, Se and Zn levels were also significantly lower, and levels of Ni, Co, and Cu were higher (p<0.001) in patients with prostate cancer than in controls. Fe levels were not significantly different in patients compared to controls (p>0.05). Our findings, together with the results of previous animal studies, suggest that the administration of vitamins A, C, and E, and Se and Zn may be beneficial in the prevention and treatment of human prostate cancer.

Topics: Aged; Aged, 80 and over; Ascorbic Acid; Cobalt; Copper; Humans; Iron; Lipid Peroxidation; Male; Malondialdehyde; Middle Aged; Nickel; Prostatic Neoplasms; Selenium; Trace Elements; Vitamin A; Vitamin E; Zinc

Vitamin E, beta-carotene, and vitamin C are micronutrient antioxidants that protect cells from oxidative damage involved in prostate carcinogenesis. In separate trials, supplemental vitamin E was associated with a decreased risk of prostate cancer among smokers and supplemental beta-carotene was associated with a decreased risk of prostate cancer among men with low baseline plasma beta-carotene levels.. We evaluated the association between intake of these micronutrient antioxidants from foods and supplements and the risk of prostate cancer among men in the screening arm of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. At baseline, trial participants completed a 137-item food frequency questionnaire that included detailed questions on 12 individual supplements. Cox proportional hazards models were used to estimate relative risks (RRs) and 95% confidence intervals (CIs). All statistical tests were two-sided.. We identified 1338 cases of prostate cancer among 29 361 men during up to 8 years of follow-up. Overall, there was no association between prostate cancer risk and dietary or supplemental intake of vitamin E, beta-carotene, or vitamin C. However, among current and recent (i.e., within the previous 10 years) smokers, decreasing risks of advanced prostate cancer (i.e., Gleason score > or = 7 or stage III or IV) were associated with increasing dose (RR for > 400 IU/day versus none = 0.29, 95% CI = 0.12 to 0.68; Ptrend = .01) and duration (RR for > or = 10 years of use versus none = 0.30, 95% CI = 0.09 to 0.96; Ptrend = .01) of supplemental vitamin E use. Supplemental beta-carotene intake at a dose level of at least 2000 microg/day was associated with decreased prostate cancer risk in men with low (below the median of 4129 microg/day) dietary beta-carotene intake (RR = 0.52, 95% CI = 0.33 to 0.81). Among smokers, the age-adjusted rate of advanced prostate cancer was 492 per 100,000 person-years in those who did not take supplemental vitamin E, 153 per 100,000 person-years in those who took more than 400 IU/day of supplemental vitamin E, and 157 per 100,000 person-years in those who took supplemental vitamin E for 10 or more years. Among men with low dietary beta-carotene intake, the age-adjusted rate of prostate cancer was 1122 per 100,000 person-years in those who did not take supplemental beta-carotene, and 623 per 100,000 person-years in those who took at least 2000 microg/day of supplemental beta-carotene.. Our results do not provide strong support for population-wide implementation of high-dose antioxidant supplementation for the prevention of prostate cancer. However, vitamin E supplementation in male smokers and beta-carotene supplementation in men with low dietary beta-carotene intakes were associated with reduced risk of this disease.

Topics: Adult; Aged; Anticarcinogenic Agents; Antioxidants; Ascorbic Acid; beta Carotene; Dietary Supplements; Humans; Incidence; Male; Mass Screening; Middle Aged; Prospective Studies; Prostatic Neoplasms; Risk Assessment; Smoking; Treatment Outcome; United States; Vitamin E

Antioxidants, such as vitamin C, are hypothesized to prevent prostate carcinogenesis by protecting the DNA from oxidative damage. We assessed whether higher prediagnostic plasma concentrations of vitamin C were associated with a lower risk of prostate cancer in a well-nourished cohort of men.. Plasma concentrations of ascorbic acid (vitamin C) were previously determined in blood specimens collected between 1984 and 1990 in men participating in the Baltimore Longitudinal Study of Aging. Total plasma ascorbic acid (L-ascorbic acid plus dehydro-L-ascorbic acid) levels were measured by using a modification of the 2,4-dinitrophenylhydrazine method. Among the 498 male participants with measured plasma vitamin C levels, 62 men were subsequently diagnosed with prostate cancer during their lifetime. Cox proportional hazards regression models were used to estimate relative risks and 95% confidence intervals for prostate cancer.. The median plasma concentration of vitamin C for the cohort was 1.17 mg/dL, which is in the normal to high range for older men. The age-adjusted relative risk of prostate cancer for the highest quartile (median = 1.47 mg/dL, range = 1.36-2.58) compared with the lowest quartile (median = 0.83 mg/dL, range = 0.15-0.98) of plasma vitamin C concentration was 1.31 (95% confidence interval 0.63 to 2.70, P for trend = 0.29). Adjustment for cigarette smoking status, body mass index, or plasma cholesterol concentration did not attenuate the results.. This small but prospective study suggests that higher plasma vitamin C concentrations within the normal physiologic range are not associated with a lower risk of prostate cancer in well-nourished men.

Topics: Aging; Antioxidants; Ascorbic Acid; Baltimore; Cohort Studies; Confidence Intervals; Humans; Longitudinal Studies; Male; Middle Aged; Oxidation-Reduction; Proportional Hazards Models; Prostatic Neoplasms; Risk Factors

Expression of the multidrug resistance (MDR) transporter P-glycoprotein (P-gp) has been demonstrated to be regulated by hypoxia-inducible factor-1alpha (HIF-1alpha) and inhibited by intracellular reactive oxygen species (ROS). Herein, P-gp and HIF-1alpha expression were investigated in multicellular prostate tumor spheroids overexpressing the ROS-generating enzyme Nox-1 in comparison to the mother cell line DU-145. In Nox-1-overexpressing tumor spheroids (DU-145Nox1) generation of ROS as well as expression of Nox-1 was significantly increased as compared to DU-145 tumor spheroids. ROS generation was significantly inhibited in the presence of the NADPH-oxidase antagonists diphenylen-iodonium chloride (DPI) and 4-(2-aminoethyl)benzenesulfonyl fluoride (AEBSF). Albeit growth kinetic of DU-145Nox1 tumor spheroids was decreased as compared to DU-145 spheroids, elevated expression of Ki-67 was observed indicating increased cell cycle activity. In DU-145Nox1 tumor spheroids, expression of HIF-1alpha as well as P-gp was significantly decreased as compared to DU-145 spheroids, which resulted in an increased retention of the anticancer agent doxorubicin. Pretreatment with the free radical scavengers vitamin E and vitamin C increased the expression of P-gp as well as HIF-1alpha in Nox-1-overexpressing cells, whereas no effect of free radical scavengers was observed on mdr-1 mRNA expression. In summary, the data of the present study demonstrate that the development of P-gp-mediated MDR is abolished under conditions of elevated ROS levels, suggesting that the MDR phenotype can be circumvented by modest increase of intracellular ROS generation.

Topics: Ascorbic Acid; ATP Binding Cassette Transporter, Subfamily B, Member 1; Biphenyl Compounds; Cell Line, Tumor; Drug Resistance, Multiple; Free Radical Scavengers; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Male; Multidrug Resistance-Associated Proteins; NADPH Oxidase 1; NADPH Oxidases; Onium Compounds; Prostatic Neoplasms; Reactive Oxygen Species; Spheroids, Cellular; Sulfones; Transcription Factors; Vitamin E

We postulated that combinations of C and E vitamins modulate the antioxidant network and blocks survivin gene expression in androgen-responsive and non-responsive human prostate cancer cell (HPCC) lines.. ALVA-101 and DU-145 cell growth and apoptosis were estimated using the Cell Titer 96 AQ and cell death detection ELISA. Reverse transcription-polymerase chain reaction, Western blot and electrophoretic mobility shift assay were used to quantify survivin mRNA, protein, nuclear factor kappa B (NF-kappaB), and activator protein-1 (AP-1).. All the tested combinations of vitamins C and E (25-100 microM, 72 hr) reduced cell growth (4-83%). Vitamin C enhanced the growth suppressive effect of vitamin E. Apoptosis was enhanced (25-45%) (vitamins = 100 microM, 24 hr). Survivin mRNA was decreased (26-29%) (vitamins = 250 microM, 24 hr), and survivin protein was decreased (>90%) (vitamins = 100 microM, 72 hr). NF-kappaB and AP-1 activities were increased (vitamins = 100 microM, 24 hr).. The combinations of vitamins C and E are potent inducers of apoptosis in HPCC and suppressers of surviving, an antiapoptotic factor.

Topics: Antioxidants; Apoptosis; Ascorbic Acid; Blotting, Western; Cell Division; Cysteine Proteinase Inhibitors; Drug Therapy, Combination; Gene Expression Regulation, Neoplastic; Humans; Inhibitor of Apoptosis Proteins; Male; Microtubule-Associated Proteins; Neoplasm Proteins; Prostatic Neoplasms; Reverse Transcriptase Polymerase Chain Reaction; Survivin; Tumor Cells, Cultured; Vitamin E

To study biologic effects of increased manganese superoxide dismutase (MnSOD) on cell behavior, we overexpressed MnSOD in a human prostate cancer cell line RWPE-2 by cDNA transfection. Stable transfectants of MnSOD showed a two- to threefold increase in MnSOD protein and enzymatic activity and a decrease in growth rate with prolonged cell population doubling times. Western blot analysis showed a 1.5- to twofold increase in the cyclin-dependent kinase inhibitor p21(Waf1) in MnSOD transfectants. Overexpression of MnSOD resulted in a seven- to eightfold increase in reduced glutathione (GSH), 18- to 26-fold increase in oxidized glutathione (GSSG), and a two- to threefold decrease in the ratio of GSH to GSSG. MnSOD-overexpressing cells showed an increase in sensitivity to the cytotoxicity of buthionine sulfoximine, a glutathione-depleting agent, and vitamin C, but a decrease in sensitivity to sodium selenite. Treatment with a superoxide dismutase (SOD) mimic MnTMPyP resulted in similar effects of MnSOD overexpression on cell responses to vitamin C and selenium. These data demonstrate that overexpression of MnSOD or treatment with SOD mimics can result in antioxidant or prooxidant effects in cells, depending on the presence of other antioxidants and prooxidants. MnSOD also has redox regulatory effects on cell growth and gene expression. These findings suggest that MnSOD and SOD mimics have the potential for cancer prevention or treatment.

Topics: Adenocarcinoma; Animals; Antioxidants; Ascorbic Acid; Blotting, Western; Cell Line, Tumor; Cell Proliferation; Cyclin-Dependent Kinase Inhibitor p21; Cyclins; DNA, Complementary; Dose-Response Relationship, Drug; Glutathione; Glutathione Peroxidase; Humans; Male; Oxidants; Oxidation-Reduction; Oxidative Stress; Oxygen; Phenotype; Plasmids; Prostatic Neoplasms; Rats; Sodium Selenite; Superoxide Dismutase; Tetrazolium Salts; Thiazoles; Transfection

Mitochondrial aconitase (mACON), an iron-requiring enzyme, is a major target of nitric oxide (NO) in cells, which causes the oxidant-mediated disruption of the [4Fe-4S] prosthetic group of the enzyme. In this study, the effect of NO on mACON enzymatic activity and gene expression were investigated.. Three NO generators, sodium nitroprusside (SNP), S-nitoso-N-acetylpenicillamine (SNAP), and 3-morpholinosydnonimine (SIN) were used to determine the regulation of mACON enzymatic activity by NO. The effect of SNP on mACON, which modulates citrate secretion and cellular bioenergetics in PC-3 cells, was investigated by determining the effect of SNP on mACON gene expression using Western blot and transient gene expression assays.. SNP upregulated mACON enzymatic activity and gene expression in PC-3 cells. However, treating cells with other NO generators, SNAP and SIN, resulted in decreased mACON enzymatic activity. The addition of ascorbic acid to the SNP treatment resulted in a decrease in mACON enzymatic activity and gene expression. Our results showed that both SNP and dibutyryl-cAMP increased the mACON promoter activity 2-fold while the effect was blocked by adding H-89. Mutation of the cAMP response element (CRE) to the AGAGCT abolished the activating effects of SNP and dibutyryl-cAMP on mACON promoter activity.. These results establish the function of nitroprusside as a signaling molecule for mACON gene expression through the cAMP signal transduction pathway in human prostatic carcinoma cells.

Topics: Aconitate Hydratase; Ascorbic Acid; Blotting, Western; Cell Line, Tumor; Cyclic AMP; Free Radical Scavengers; Gene Expression; Humans; Male; Molsidomine; Nitric Oxide Donors; Nitroprusside; Prostatic Neoplasms; Reverse Transcriptase Polymerase Chain Reaction; RNA, Neoplasm; S-Nitroso-N-Acetylpenicillamine; Signal Transduction

The mitochondrial aconitase (mACON) containing a [4Fe-4S] cluster is regarded as the key enzyme for citrate oxidation in the epithelial cells of human prostate. In vitro studies using the human prostatic carcinoma cells, PC-3 cells, found that both hemin and ferric ammonium citrate (FAC) significantly increased mACON enzymatic activity and gene expression. The effect of FAC on mACON was enhanced 2-fold by co-treating with ascorbic acid but blocked by co-treating with iron chelator, deferoxamine mesylate. Hemin treatments blocked 30% of citrate secretion from PC-3 cells but upregualted 2-fold of intracellular ATP biosynthesis. Results from reporter assay by using a cytomegalovirus enhance/promoter driven luciferase mRNA ligated to the iron response element (IRE) of mACON as a reporter construct demonstrated that modulation of FAC on gene translation of mACON gene is dependent on the IRE. Transient gene expression assays indicated that upregulation of mACON gene transcription by FAC may through the putative antioxidant response element (ARE) signal pathway. This study provides the first evidence of the biologic mechanism of human mACON gene translation/transcription and suggests a regulatory link between the energy utilization and the iron metabolism in human prostatic carcinoma cells.

Topics: Aconitate Hydratase; Adenosine Triphosphate; Ascorbic Acid; Base Sequence; Cell Line, Tumor; Cell Proliferation; Chelating Agents; Citrates; Deferoxamine; Dose-Response Relationship, Drug; Ferric Compounds; Gene Expression Regulation, Neoplastic; Genes, Reporter; Genetic Vectors; Hemin; Humans; Immunoblotting; Iron; Male; Mitochondria; Molecular Sequence Data; Mutagenesis, Site-Directed; Prostatic Neoplasms; Protein Biosynthesis; Quaternary Ammonium Compounds; Signal Transduction; Transcription, Genetic; Up-Regulation

Once prostate cancer has metastasized, current treatment methods are generally ineffective. Due to the reported anti-tumor properties of specific nutrients, we investigated the effect of a unique formulation (NS) of lysine, proline, arginine, ascorbic acid, and epigallocatechin gallate on human prostate cancer cell lines: PC-3, DU145 (androgen insensitive) and LNCaP (androgen sensitive), by measuring cell proliferation, MMP expression, and invasion potential. Cell lines DU145, PC-3, and LNCaP were treated at near confluence with NS at various concentrations. Cell proliferation was measured by MTT assay after 24 hours, MMP expression was measured by gelatinase zymography in condition media, and invasion activity was measured by Matrigel. The nutrient mixture did not significantly inhibit PC-3 cell proliferation at 50 microg/ml, but showed significant antiproliferative effect at 500 ug/ml. When treated with NS, proliferation of LNCaP cells was inhibited by 80% of control at 100 microg/ml. NS showed dose-dependent inhibition of DU145 cell proliferation with 47% reduction at 1000 microg/ml. NS showed a dose-dependent inhibition of both MMP-2 and MMP-9 expression by PC-3 cells and MMP-9 expression by PMA-treated (200 ng/ml) DU145 cells. Neither MMP-2 nor MMP-9 gelatinolytic activity was detected in LNCaP cell culture. Invasion of DU145 and LNCaP cells through Matrigel was completely inhibited at 500 microg/ml and PC-3 at 1000 microg/ml. Inhibition of MMP expression and invasion suggests the mixture of nutrients studied is a potent, natural anticancer agent for the treatment of prostate cancer.

Topics: Antioxidants; Arginine; Ascorbic Acid; Catechin; Cell Line, Tumor; Cell Proliferation; Chemistry, Pharmaceutical; Collagen; Dose-Response Relationship, Drug; Drug Combinations; Drug Synergism; Formazans; Humans; Laminin; Lysine; Male; Matrix Metalloproteinases; Neoplasm Invasiveness; Proline; Prostatic Neoplasms; Proteoglycans; Tetrazolium Salts

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 effects of vitamin C (VC) on androgen receptor (AR)-mediated functions in a human prostate cancer cell line, Los Angeles prostate cancer (LAPC-4). VC is an essential dietary substance in the maintenance and preservation of vital functions in humans. However, the role of VC in prostate cancer remains to be elucidated.. Cell proliferation and the expression of two well-known androgen regulated proteins, prostate-specific antigen and human glandular kallikrein-2, were studied in the presence of VC.. In the presence of androgen and VC, both cell growth and the expression of prostate-specific antigen and human glandular kallikrein-2 proteins were decreased. Moreover, AR-mediated transcription activity of the prostate-specific antigen gene was suppressed with VC, similar to the phenomenon observed when cells were treated with hydrogen peroxide. These effects were reversed with catalase. However, additional studies did not reveal changes in the expression level of AR protein or its androgen-binding activity with the addition of VC.. The results of our study suggest that the pro-oxidant property of VC might be one of the mechanisms by which it modulates AR-mediated function in LAPC-4 cells.

Topics: Adenocarcinoma; Androgens; Anticarcinogenic Agents; Ascorbic Acid; Cell Differentiation; Cell Division; Gene Expression Regulation, Neoplastic; Genes, Reporter; Humans; Male; Neoplasm Proteins; Neoplasms, Hormone-Dependent; Prostate-Specific Antigen; Prostatic Neoplasms; Receptors, Androgen; Tissue Kallikreins; Transcription, Genetic; Transfection; Tumor Cells, Cultured

Results of a randomized controlled trial have suggested a protective effect of selenium against prostate cancer. Few other prospective studies have been conducted to confirm or refute this. The association between prostate cancer and baseline toenail selenium level was evaluated in the Netherlands Cohort Study, conducted among 58,279 men, aged 55-69 years at entry. In September 1986, the cohort members completed a questionnaire on risk factors for cancer and provided toenail clippings for determination of baseline selenium status. After 6.3 years of follow-up, 540 incident prostate carcinoma cases and 1,211 subcohort members with complete toenail selenium data were available for case-cohort analyses. In multivariate survival analysis, an inverse association between toenail selenium level and prostate cancer risk was observed. Incidence rate ratios in increasing selenium quintiles were 1.00 (ref), 1.05, 0.69, 0.75, and 0.69 (95% confidence interval, 0.48-0.99), respectively (P-trend=0.008). This association persisted after exclusion of cases diagnosed during early follow-up. The inverse association was more pronounced in ex-smokers than current smokers, and unclear in never-smokers. Analysis of effect modification by intake of antioxidant vitamins C, E, and the carotenoids alpha-carotene, beta-carotene, beta-cryptoxanthin, lycopene, and lutein/zeaxanthin showed a strong, significant interaction with beta-cryptoxanthin, and to a lesser extent with vitamin C. These results confirm the hypothesis that higher selenium intake may reduce prostate cancer risk. Future research on optimum dose level is needed.

Topics: Aged; Antioxidants; Ascorbic Acid; beta Carotene; Carotenoids; Cohort Studies; Cryptoxanthins; Follow-Up Studies; Humans; Lycopene; Male; Middle Aged; Nails; Netherlands; Prospective Studies; Prostatic Neoplasms; Risk Factors; Selenium; Smoking; Surveys and Questionnaires; Vitamin E; Xanthophylls

The roles of retinol, vitamins C and E, and carotenoids as risk factors for prostate carcinoma are still questionable. We evaluated these in the Netherlands Cohort Study.. The cohort study consisted of 58,279 men ages 55-69 years at baseline in 1986. After 6.3 years of follow-up, 642 incident prostate carcinoma cases were available for analysis. Intakes of retinol, vitamins C and E, and several carotenoids were measured by means of a 150-item semi-quantitative food-frequency questionnaire.. In multivariate analyses a positive association with prostate cancer risk was observed for intake of beta-cryptoxanthin. Rate ratios (RRs) in increasing quintiles were 1.00 (ref), 0.94, 1.01, 1.16, 1.41; p-trend < 0.01. For intake of retinol, vitamins C and E and other carotenoids (alpha-carotene, beta-carotene, lycopene, and lutein/zeaxanthin) no effect on overall prostate cancer risk was found. RRs for vitamin supplement use were decreased, but not significantly. Among nondrinkers, nonsignificant inverse associations were observed for intake of retinol, alpha-carotene, and beta-carotene (RRs, highest vs lowest quintile, were 0.23, 0.60, and 0.76, respectively). Among drinkers, beta-cryptoxanthin was positively associated (RR highest vs lowest quintile = 1.40).. These data show a positive association between beta-cryptoxanthin and prostate cancer risk. Our study also shows inverse associations for retinol, alpha-carotene, and beta-carotene among nondrinkers; this suggests an interaction between vitamins and alcohol consumption, which needs confirmation. Lycopene was not associated with prostate cancer.

Topics: Aged; Alcohol Drinking; Antioxidants; Ascorbic Acid; beta Carotene; Carotenoids; Cohort Studies; Confidence Intervals; Cryptoxanthins; Feeding Behavior; Humans; Male; Middle Aged; Multivariate Analysis; Netherlands; Prospective Studies; Prostatic Neoplasms; Risk Factors; Surveys and Questionnaires; Vitamin A; Vitamin E; Xanthophylls

Human prostate cancer cells (DU145) implanted into nude mice are deficient in DNase activity. After administration of a vitamin C/vitamin K(3) combination, both alkaline DNase (DNase I) and acid DNase (DNase II) activities were detected in cryosections with a histochemical lead nitrate technique. Alkaline DNase activity appeared 1 hr after vitamin administration, decreased slightly until 2 hr, and disappeared by 8 hr after treatment. Acid DNase activity appeared 2 hr after vitamin administration, reached its highest levels between 4 and 8 hr, and maintained its activity 24 hr after treatment. Methyl green staining indicated that DNase expression was accompanied by a decrease in DNA content of the tumor cells. Microscopic examination of 1-microm sections of the tumors indicated that DNase reactivation and the subsequent degradation of DNA induced multiple forms of tumor cell death, including apoptosis and necrosis. The primary form of vitamin-induced tumor cell death was autoschizis, which is characterized by membrane damage and the progressive loss of cytoplasm through a series of self-excisions. These self-excisions typically continue until the perikaryon consists of an apparently intact nucleus surrounded by a thin rim of cytoplasm that contains damaged organelles.

Topics: Animals; Ascorbic Acid; Cell Death; Coloring Agents; Deoxyribonucleases; Drug Synergism; Enzyme Reactivators; Histocytochemistry; Humans; Lead; Male; Methyl Green; Mice; Mice, Nude; Microscopy, Electron; Nitrates; Prostatic Neoplasms; Vitamin K; Xenograft Model Antitumor Assays

To explore more effective treatment for hormone-refractory prostate cancer, we investigated the potential antitumor effect of beta-glucan, a polysaccharide of the Maitake mushroom, on prostatic cancer cells in vitro.. Human prostate cancer PC-3 cells were treated with various concentrations of the highly purified beta-glucan preparation Grifron-D(R) (GD), and viability was determined at 24 h. Lipid peroxidation (LPO) assay and in situ hybridization (ISH) were performed to unravel the antitumor mechanism of GD.. A dose-response study showed that almost complete (>95%) cell death was attained in 24 h with GD > or = 480 microg/mL. Combinations of GD in a concentration as low as 30 to 60 microg/mL with 200 microM vitamin C were as effective as GD alone at 480 microg/mL, inducing >90% cytotoxic cell death. Simultaneous use with various anticancer drugs showed little potentiation of their efficacy except for the carmustine/GD combination (approximately 90% reduction in cell viability). The significantly (twofold) elevated LPO level and positive ISH staining of GD-treated cells indicated oxidative membrane damage resulting in apoptotic cell death.. A bioactive beta-glucan from the Maitake mushroom has a cytotoxic effect, presumably through oxidative stress, on prostatic cancer cells in vitro, leading to apoptosis. Potentiation of GD action by vitamin C and the chemosensitizing effect of GD on carmustine may also have clinical implications. Therefore, this unique mushroom polysaccharide may have great a potential as an alternative therapeutic modality for prostate cancer.

Topics: Agaricales; Androgens; Antineoplastic Agents; Apoptosis; Ascorbic Acid; Cell Division; Cell Survival; Dose-Response Relationship, Drug; Glucans; Humans; Lipid Peroxidation; Male; Prostatic Neoplasms; Tumor Cells, Cultured

Prostate cancer has one of the highest incidence rates of all cancers. Vitamin intake and tobacco use may have an impact on incidence and mortality, but epidemiologic evidence is scarce and inconsistent.. Plasma vitamins C, E, retinol, and carotene were measured in 1971-1973 in 2,974 men working in Basel, Switzerland. In 1990, the vital status of all participants was assessed.. Two hundred and ninety men had died from cancer, including 30 with prostate cancer. On average, prostate cancer cases were 15 years older and smoked slightly more frequently than survivors. The mean values of plasma carotene, and of vitamin C, were nonsignificantly lower in prostate cancer cases than in survivors. After calculation of relative risk using the Cox model with exclusion of mortality during the first 2 years of follow-up, low vitamin E levels in smokers were related to an increased risk for prostate cancer. Relative risks of low vitamin C and carotene levels were about 1. A slightly but nonsignificantly increased risk was observed for low levels of retinol.. Given the profound implication if the risk of prostatic cancer could be reduced, the relationship with vitamin E and smoking requires further study.

Topics: Ascorbic Acid; Carotenoids; Follow-Up Studies; Humans; Male; Prostatic Neoplasms; Risk Factors; Smoking; Survivors; Switzerland; Treatment Outcome; Vitamin A; Vitamin E; Vitamins

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

Studies have described the protective role of vitamin C (ascorbic acid) in certain types of cancer. In this study, we report the effects of vitamin C treatment of two androgen independent prostate cancer cell lines from human (PC3) and rat (Mat-Ly-Lu or MLL) sources. In vitro treatment of PC3 and MLL with sodium ascorbate acid (0-10 mM) resulted in a decrease in cell viability and thymidine incorporation into DNA. These effects of vit. C were dose and time dependent. Ascorbate induced these changes through the production of hydrogen peroxide since addition of catalase (100-300 units/ml), an enzyme that degrades hydrogen peroxide, inhibited the effects of ascorbate on these cell lines. In contrast, superoxide dismutase, an enzyme that dismutates superoxide and generates hydrogen peroxide did not prevent ascorbate-induced changes emphasizing the involvement of reactive oxygen species (ROS) in cellular damage. That singlet oxygen scavengers such as sodium azide and hydroquinone, hydroxyl radical scavengers such as D-mannitol and DL-alpha-tocopherol did not counteract the effects of ascorbate on thymidine incorporation suggests that these free radicals are not involved in cellular damage. In conclusion, these results suggest that vitamin C inhibits tumor growth by virtue of producing reactive oxygen species. These results suggest that ascorbate is a potent anticancer agent for prostate cancer cells.

Topics: Animals; Ascorbic Acid; Catalase; Cell Division; Cell Survival; DNA Replication; Dose-Response Relationship, Drug; Flow Cytometry; Humans; Male; Neoplasms, Hormone-Dependent; Prostatic Neoplasms; Rats; Reactive Oxygen Species; Superoxide Dismutase; Tumor Cells, Cultured

Prostate cancer is a disease associated with aging. Also commonly associated with increasing age is a shift in the prooxidant-antioxidant balance of many tissues toward a more oxidative state, i.e., increased oxidative stress. We hypothesize that androgen exposure, which has long been associated with the development of prostate cancer, may be a means by which the prooxidant-antioxidant balance of prostate cells is altered.. Using established prostate carcinoma cell lines, we studied the effect of androgens on various parameters of oxidative state (e.g., generation of hydrogen peroxide and hydroxyl radicals, lipid peroxidation, and oxygen consumption) and antioxidant defense mechanisms (e.g., the glutathione system and catalase).. The androgen-responsive LNCaP and the androgen-independent DU145 prostate carcinoma cell lines were exposed to 5 alpha-dihydrotestosterone (DHT) and to the synthetic androgen R1881. The cellular proliferation responses were measured by use of a fluorometric assay to quantitate the amount of DNA. The generation of reactive oxygen species was measured by use of 2',7'-dichlorofluorescin diacetate, a dye that fluoresces in the presence of hydrogen peroxide or hydroxyl radicals. Lipid peroxidation was quantitated by use of a chromogen specific for malonaldehyde and 4-hydroxy-2(E)-nonenal. General mitochondrial activity was determined by assaying 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction. A Clark-type electrode was used to assess oxygen consumption per cell. Intracellular glutathione concentrations and the activities of catalase and gamma-glutamyl transpeptidase were measured spectrophotometrically. All P values resulted from two-sided tests.. DHT at less than 1 to 100 nM (a concentration range encompassing the physiologic levels of DHT considering all ages) and R1881 at 0.1-1 nM concentrations were effective in inducing in LNCaP cells comparable proliferative responses and changes in oxidative stress. In contrast, neither DHT nor R1881 had any effect on the oxidative stress in DU145 cells. The mitochondrial activity in LNCaP cells, as measured by MTT reduction, was significantly elevated above the levels of the untreated controls by DHT (0.1-1000 nM) and R1881 (0.05-1 nM) (P < .001 in both). Oxygen consumption and catalase activity were increased in LNCaP cells in the presence of 1 nM R1881 by 60% and 40%, respectively, over the values in the untreated control cells (P < .03 and P < .01, respectively). The same concentration of R1881 resulted in a decrease in intracellular glutathione concentrations and an increase in gamma-glutamyl transpeptidase activity in LNCaP cells. Treatment with the oxidizing agents H2O2 and menadione produced an increase in gamma-glutamyl transpeptidase activity in LNCaP cells, whereas treatment with the antioxidant compound ascorbic acid (100 mM) reduced the oxidative stress produced in LNCaP cells by 1 nM R1881 and completely blocked the gamma-glutamyl transpeptidase activity.. Physiologic levels of androgens are capable of increasing oxidative stress in androgen-responsive LNCaP prostate carcinoma cells. The evidence suggests that this result is due in part to increased mitochondrial activity. Androgens also alter intracellular glutathione levels and the activity of certain detoxification enzymes, such as gamma-glutamyl transpeptidase, that are important for maintenance of the cellular prooxidant-antioxidant balance.

Topics: Androgens; Ascorbic Acid; Catalase; Cell Division; Dihydrotestosterone; Free Radicals; gamma-Glutamyltransferase; Glutathione; Humans; Hydrogen Peroxide; Lipid Peroxidation; Male; Metribolone; Mitochondria; Oxidation-Reduction; Oxygen; Oxygen Consumption; Prostatic Neoplasms; Testosterone Congeners; Time Factors; Tumor Cells, Cultured

Topics: Ascorbic Acid; beta Carotene; Follow-Up Studies; Humans; Incidence; Male; Proportional Hazards Models; Prostatic Neoplasms; Reproducibility of Results; Risk Factors; Time Factors

Many studies describe the protective role of vitamin C (ascorbic acid) against cancer development and in treatment of established cancer. The present study investigated whether ascorbic acid demonstrates a therapeutic benefit for prostate cancer.. Androgen-independent (DU145) and androgen-dependent (LNCaP) human prostate cancer cell lines were both treated in vitro with vitamin C (0-10 mM). Cell counts, cell viability, and thymidine incorporation into DNA were determined.. Treatment of DU145 and LNCaP cells with vitamin C resulted in a dose- and time-dependent decrease in cell viability and thymidine incorporation into DNA. Vitamin C induced these changes through the production of hydrogen peroxide; addition of catalase (100-300 units/ml), an enzyme that degrades hydrogen peroxide, inhibited the effects of ascorbic acid. Superoxide dismutase, an enzyme that dismutates superoxide and generates hydrogen peroxide, did not prevent decreases in cell number and DNA synthesis, suggesting further the involvement of hydrogen peroxide in vitamin C-induced changes. These results clearly indicate that reactive oxygen species (ROS) are involved in vitamin C-induced cell damage. However, that singlet oxygen scavengers such as sodium azide and hydroquinone and hydroxyl radical scavengers such as D-mannitol and DL-alpha-tocopherol did not counteract the effects of ascorbic acid on thymidine incorporation suggests that vitamin C-induced changes do not occur through the generation of these ROS.. Vitamin C inhibits cell division and growth through production of hydrogen peroxide, which damages the cells probably through an as yet unidentified free radical(s) generation/mechanism. Our results also suggest that ascorbic acid is a potent anticancer agent for prostate cancer cells.

Topics: Androgens; Antineoplastic Agents; Ascorbic Acid; Azides; Cell Count; Cell Survival; DNA, Neoplasm; Dose-Response Relationship, Drug; Free Radicals; Humans; Hydrogen Peroxide; Hydroquinones; Hydroxyl Radical; In Vitro Techniques; Male; Prostatic Neoplasms; Sodium Azide; Superoxide Dismutase; Thymidine; Tritium; Tumor Cells, Cultured

In order to study the relationship between dietary nutrients intakes and prostate cancer, 1 : 1 matched case-control study was carried out with 102 patients suffered from histologically confirmed prostate cancer and 102 healthy controls. Total calories and 11 nutrients including protein, lipid and carbohydrates were calculated based on the mean food intakes in the latest 3 days. Analyzed by matched t-test and conditional logistic regression method, the results showed that high intakes of lipid, carbohydrates, and retinol increased the risk of prostate cancer, but vitamin C and vitamin B1 decreased the risk of prostate cancer. The multivariable adjusted ORs were 1.65 (95% confident interval (CI) 1.39-1.96) for lipid, 1.22 (95% CI 1.13-1.31) for carbohydrates, 3.21 (95% CI 2.18-4.75) for retinol, 0.61 (95% CI 0.6-0.80) for vitamin C, and 0.029 (95% CI 0.009-0.09) for vitamin B1. The authors discussed the possible mechanism of dietary nutrients contributing to the risk of prostate cancer.

Topics: Adult; Aged; Aged, 80 and over; Ascorbic Acid; Case-Control Studies; China; Dietary Fats; Humans; Male; Middle Aged; Nutrition Surveys; Prostatic Neoplasms; Regression Analysis; Risk Factors; Thiamine; Vitamin A

Plasma vitamins C, E, retinol and carotene were measured in 1971-1973 in 2,974 men working in Basel Switzerland. In 1990, the vital status of all participants was assessed. A total of 290 men had died from cancer during the 17 years of follow-up, including 87 with lung cancer, 30 with prostate cancer, 28 with stomach cancer and 22 with colon cancer. Overall mortality from cancer was associated with low mean plasma levels of carotene (adjusted for cholesterol) and of vitamin C. Lung and stomach cancers were associated with low mean plasma carotene level. After calculation of the relative risk, using the Cox model, with exclusion of mortality during the first 2 years of follow-up, simultaneously low levels of plasma carotene (below quartile I) and lipid-adjusted retinol were related to a significantly increased mortality risk for all cancers and for lung cancer. Simultaneously, low levels of plasma vitamin C and lipid-adjusted vitamin E also were associated with a significantly increased risk for lung cancer. Additionally, low vitamin E levels in smokers were related to an increased risk for prostate cancer. It is concluded that low plasma levels of the vitamins C, E, retinol and carotene are related to increased risk of subsequent overall and lung-cancer mortality and that low levels of vitamin E in smokers are related to an increased risk of prostate-cancer mortality.

Topics: Adult; Aged; Antioxidants; Ascorbic Acid; Carotenoids; Follow-Up Studies; Humans; Male; Middle Aged; Neoplasms; Prospective Studies; Prostatic Neoplasms; Vitamin A; Vitamin E; Vitamins

Dietary factors are likely candidates for important determinants of prostatic cancer risk. Among the most investigated nutritional factors have been antioxidants. We evaluated dietary beta-carotene and vitamin C in relation to subsequent risk of prostate cancer in a prospective study of 1,899 middle-aged men. We combined prostate cancer cases diagnosed in the first 24 years of follow-up with incident cases identified from the Health Care Financing Administration hospitalization and outpatient files during an additional 6-year follow-up period. We obtained death certificates for all decedents. During the 30-year follow-up, prostate cancer developed in 132 men. There was no indication that consumption of beta-carotene or vitamin C was related to increased or decreased risk of prostate cancer. Relative risks for highest vs lowest quartiles of beta-carotene and vitamin C intake were 1.27 [95% confidence interval (CI) = 0.75-2.14] and 1.03 (95% CI = 0.59-1.60), respectively, after adjustment for age, number of cigarettes smoked per day, dietary cholesterol and saturated fat, alcohol consumption, total energy intake, and occupation. Associations between intake of these nutrients and risk of prostate cancer differed depending on whether the cancer was diagnosed during the first 19 years of follow-up or the next 11 years of follow-up. Overall survival over the 30 years of follow-up was positively associated with intake of beta-carotene and vitamin C.

Topics: Adult; Ascorbic Acid; beta Carotene; Diet; Health Behavior; Humans; Illinois; Incidence; Male; Middle Aged; Prospective Studies; Prostatic Neoplasms; Risk Factors; Socioeconomic Factors

Transmission and scanning electron microscopy and flow cytometry were employed to characterize the cytotoxic effects of vitamin C (VC), vitamin K3 (VK3), or VC-VK3 combinations on a human prostate carcinoma cell line (DU145) following a 1-h vitamin treatment and a 24-h incubation in culture medium. Cells exposed to VC exhibited membranous blebs, aberrant microvillar morphology, mitochondria with swollen cristae and intramitochondrial deposits, as well as nucleoli with segregated components. VK3-treated cells displayed a damaged cytoskeleton and membranes, a cytoplasm which contained large lumen, condensed polysomes, and severely damaged mitochondria with residual bodies, and nuclei which exhibited chromatic condensation, pyknosis, and karyolysis. VC-VK3-treated cells exhibited characteristics consistent with necrosis, i.e. swollen mitochondria and swollen, achromatic nuclei with marginated chromatin and intact envelopes, while other cells displayed characteristics consistent with apoptosis, i.e. expulsion of organelle-containing blebs, margination of nuclear chromatin, and segregation of nucleolar components. Vitamin treatment also decreased DNA synthesis, induced a S/G2 block in the cell cycle, and resulted in the accumulation of fragmented DNA. These results suggested that increased oxidative stress, subsequent membrane damage, and DNA fragmentation were responsible for enhanced cytotoxicity of the vitamin combination.

Topics: Antineoplastic Combined Chemotherapy Protocols; Ascorbic Acid; DNA; Drug Synergism; Flow Cytometry; Hemostatics; Humans; Male; Microscopy, Electron; Microscopy, Electron, Scanning; Prostatic Neoplasms; Thymidine; Tritium; Tumor Cells, Cultured; Vitamin K

Vitamins C, K3 (VC, VK3) and a VC/VK3 combination with a VC:VK3 ratio of 100:1 were assayed for their antitumour activity against two human prostatic carcinoma cell lines. Co-administration of the vitamins enhanced the antitumour activity 5- to 20-fold even with a 1 h exposure time. While exogenous catalase destroyed the antitumour activity, hydrogen peroxide-induced lipid peroxidation was negligible. Analysis of cellular ATP and thiol levels as well as DNA and protein synthesis revealed: a transient increase in ATP production, a decrease in DNA synthesis, an increase in protein synthesis and a decrease in thiol levels. These results suggested that the increased cytotoxicity of the vitamin combination was due to redox cycling and increased oxidative stress.

Topics: Adenosine Triphosphate; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Ascorbic Acid; Carcinoma; Catalase; DNA, Neoplasm; Humans; Hydrogen Peroxide; Lipid Peroxidation; Male; Neoplasm Proteins; Prostatic Neoplasms; Sulfhydryl Compounds; Tumor Cells, Cultured; Vitamin K

A MTT/formazan assay was used to evaluate the antitumor activity of vitamin C (Vit C), vitamin K3 (Vit K3), or vitamin C:vitamin K3 combinations against a human prostatic carcinoma cell line (DU145). Both Vit C and Vit K3 alone exhibited antitumor activity, but only at elevated doses. When Vit C and Vit K3 were combined at a C:K3 ratio of 100:1 and administered to the carcinoma cells, the 50% cytotoxic concentrations (CD50) of the vitamins decreased 10- to 60-fold. Subsequently, the DU145 cells were examined with transmission and scanning electron microscopy (TEM and SEM) following a 1 hour treatment with Vit C, Vit K3, or Vit C/K3 combined at their 50% cytotoxic dose. Our morphological data suggest that vitamin treatment with individual vitamins affects the cytoskeleton, the mitochondria, and other membranous components of the cell. Treatment with the vitamin combination appears to potentiate the effects of the individual vitamin treatment. Specifically, there are abundant necrotic cells. The surviving cells display morphological defects characteristic of cell injury.

Topics: Antineoplastic Agents; Ascorbic Acid; Carcinoma; Cell Membrane; Coloring Agents; Cytoskeleton; Drug Synergism; Drug Therapy, Combination; Humans; Male; Microscopy, Electron; Microscopy, Electron, Scanning; Mitochondria; Prostatic Neoplasms; Tetrazolium Salts; Thiazoles; Tumor Cells, Cultured; Vitamin K

Topics: Acute Disease; Acute Kidney Injury; Adenocarcinoma; Anuria; Ascorbic Acid; Humans; Infusions, Intravenous; Kidney Calculi; Male; Middle Aged; Oxalates; Prostatic Neoplasms

In order to learn about the influence of dietary factors and obesity on prostatic cancer in our environment, a case-control study was performed. The group of cases consisted of 90 men histologically diagnosed with prostatic cancer in the 'La Paz' hospital (Madrid) during the 4-year period of 1983-1987. The controls were 180 men selected to obtain a random sample of males from the same hospital, stratified according to age and date of admission as compared with the prostatic cancer patients. The results of the study revealed that a diet rich in animal fats as well as high in meat consumption increased the risk of prostatic cancer. Low ingestion of vitamin A or vitamin C and obesity were unassociated to the disease.

Topics: Aged; Aged, 80 and over; Ascorbic Acid; Case-Control Studies; Diet; Dietary Fats; Humans; Male; Meat; Middle Aged; Obesity; Prostatic Neoplasms; Vitamin A

This report presents preliminary findings from 3 case-control studies in Hawaii in which we are examining the relationship of dietary vitamin A and ascorbic acid intake to the risk for cancers of the lung, bladder, and prostate. All 3 studies involved home interviews of cancer patients and neighborhood controls and use of quantitative dietary history method. In the lung cancer study, we found an inverse dose-response effect for total vitamin A intake in males only, with an odds ratio of 1.8 (P less than .05) for the lowest intake quartile relative to the highest; we found no association for ascorbic acid. In the bladder cancer study, we found lower (but not statistically significant) mean intakes of both vitamins in patients compared with controls, with the effect stronger for ascorbic acid. In the prostate cancer study, no effect was detected for total vitamin A or ascorbic acid in men less than 70 years old, but a direct association of vitamin A only with a dose-response gradient was found for men 70 years or older (odds ratio = 1.87; P less than .05, for the highest relative to the lowest intake quartile). Our findings at present indicate that vitamin A has a protective effect against lung and bladder cancers but not against prostate cancer and that ascorbic acid has a protective effect against bladder cancer as well. In our later analyses, we will examine the possibility that the effects of vitamin A vary with histologic type and that this may account for the lack of an association with lung cancer in women.

Topics: Ascorbic Acid; Diet; Ethnicity; Female; Hawaii; Humans; Japan; Lung Neoplasms; Male; Prostatic Neoplasms; Registries; Risk; Urinary Bladder Neoplasms; Vitamin A; White People

This one-to-one, age- and race-matched case-control study involved 181 histologically confirmed black prostate cancer patients and 181 controls seen at three major hospitals in Washington, DC, during the period 1979-1982. Personal interviews were conducted to obtain the number of times food items of specified serving size were consumed per week by cases and controls during the age periods 30-49 and 50 years and older. Then the average daily consumption of each of 18 nutrients per 1,000 calories was calculated. There was risk enhancement associated with increased intake of proteins, total fat, saturated fat, oleic acid, and vitamin A during the age period 30-49 years. The association was highly significant for vitamin A and approached statistical significance for the other four nutrients. A hypothesis based on disturbance of the zinc-retinol binding protein-vitamin A axis was put forward to explain the relative risk enhancement effect of vitamin A on prostate cancer.

Topics: Adult; Age Factors; Ascorbic Acid; Black or African American; Diet; Dietary Fats; Dietary Proteins; Humans; Male; Middle Aged; Nutritional Physiological Phenomena; Oleic Acids; Prostate; Prostatic Neoplasms; Retinol-Binding Proteins; Risk; Vitamin A; Zinc

The influence of external abdominal irradiation and cytostatic therapy on the vitamin status was studied in patients with cancer of the uterus, bladder or prostate and in patients with malignant lymphoma. It was found that the vitamin status of these patients at the beginning of therapy in general was adequate, though vitamin A and vitamin D levels were reduced. During radiotherapy decreases of vitamin E, vitamin C, vitamin B12 and folic acid levels were observed. Chemotherapy caused a decrease of the folic acid levels after a few months. No clinical symptoms of vitamin deficiency were observed.

Topics: Ascorbic Acid; Calcifediol; Female; Humans; Lymphoma; Male; Neoplasms; Prostatic Neoplasms; Urinary Bladder Neoplasms; Uterine Neoplasms; Vitamin A; Vitamin B 12; Vitamin E; Vitamins

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

Topics: Ascorbic Acid; Blood; Carcinoma; Catalase; Conductometry; Dialysis; Edetic Acid; Erythrocytes; Ethylmaleimide; Hemolysis; Hot Temperature; Humans; Kidney; Liver; Lung Neoplasms; Male; Neoplasms; Prostatic Neoplasms; Stomach Neoplasms; Tissue Extracts; Triazoles