beta-carotene and Colonic-Neoplasms

Tumours in rodent and human colon share many histological and genetic features. To know if rodent models of colon carcinogenesis are good predictors of chemopreventive efficacy in humans, we conducted a meta-analysis of aspirin, beta-carotene, calcium, and wheat bran studies. Controlled intervention studies of adenoma recurrence in human volunteers were compared with chemoprevention studies of carcinogen-induced tumours in rats, and of polyps in Min (Apc(+/-)) mice: 6714 volunteers, 3911 rats and 458 mice were included in the meta-analyses. Difference between models was small since most global relative risks were between 0.76 and 1.00. A closer look showed that carcinogen-induced rat studies matched human trials for aspirin, calcium, carotene, and were compatible for wheat bran. Min mice results were compatible with human results for aspirin, but discordant for calcium and wheat bran (no carotene study). These few results suggest that rodent models roughly predict effect in humans, but the prediction is not accurate for all agents. Based on three cases only, the carcinogen-induced rat model seems better than the Min mouse model. However, rodent studies are useful to screen potential chemopreventive agents, and to study mechanisms of carcinogenesis and chemoprevention.

Topics: Animals; Aspirin; beta Carotene; Calcium; Carcinogens; Colonic Neoplasms; Dietary Fiber; Humans; Mice; Models, Animal; Randomized Controlled Trials as Topic; Rats; Rodentia; Sensitivity and Specificity

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

The intra- and interindividual variations and season and center effects were estimated from a series of serum carotenoid concentrations in the Polyp Prevention Trial (PPT) participants.. Fasting blood was collected annually for 4 years in all 1905 participants, and a subcohort of 901 participants were selected within each (of eight) center(s), by gender and dietary arm of the study, for measurement of five major carotenoid peaks. Using variance of component methods, the variation in serum carotenoid concentrations about the underlying mean was partitioned into explanatory components attributed to various sources.. The contributions of the inter- and intraindividual variances to the overall variation in carotenoid concentrations were in the range of 61-70 and 20-35%, respectively, whereas center and center-by-season effects provided 2.6-9.5 and 0.2-1.4%, respectively. The highest percent (35%) of intraindividual variation was exhibited by lycopene, and the highest percent (70% apiece) of interindividual variation was exhibited by lutein/zeaxanthin and beta-carotene. Serum lycopene had the highest ratio of intra- to interindividual variation of 0.57, whereas lutein had the lowest ratio of 0.29. We estimate that the ratio of intra- to interindividual variance around the mean carotenoid concentration can be reduced greatly by collecting 3-4 compared to 1 blood measurement in large-scale trials like the PPT.. In the largest study of components of variation in individuals at high risk for colorectal cancer, the largest contributors to variation in serum carotenoid concentrations were intra- and interindividual effects followed by center and center-by-season effects.

Topics: Adenoma; beta Carotene; Carotenoids; Colonic Neoplasms; Cryptoxanthins; Diet; Female; Humans; Lutein; Lycopene; Male; Middle Aged; Neoplasm Recurrence, Local; Risk Factors; Seasons; Xanthophylls; Zeaxanthins

High intakes of carotenoid-rich fruits and vegetables are associated with a reduced risk of various cancers including colon cancer. A human intervention study with carrot and tomato juice should show whether a diet rich in carotenoids, especially high in beta-carotene and lycopene, can modify luminal processes relevant to colon carcinogenesis. In a randomised cross-over trial, twenty-two healthy young men on a low-carotenoid diet consumed 330 ml tomato or carrot juice per d for 2 weeks. Intervention periods were preceded by 2-week depletion phases. At the end of each study period, faeces of twelve volunteers were collected for chemical analyses and use in cell-culture systems. Consumption of carrot juice led to a marked increase of beta-carotene and alpha-carotene in faeces and faecal water, as did lycopene after consumption of tomato juice. In the succeeding depletion phases, carotenoid contents in faeces and faecal water returned to their initial values. Faecal water showed high dose-dependent cytotoxic and anti-proliferative effects on colon adenocarcinoma cells (HT29). These effects were not markedly changed by carrot and tomato juice consumption. Neither bile acid concentrations nor activities of the bacterial enzymes beta-glucosidase and beta-glucuronidase in faecal water changed after carrot and tomato juice consumption. Faecal water pH decreased only after carrot juice consumption. SCFA were probably not responsible for this effect, as SCFA concentrations and profiles did not change significantly. In summary, in the present study, 2-week interventions with carotenoid-rich juices led only to minor changes in investigated luminal biomarkers relevant to colon carcinogenesis.

Topics: Adult; beta Carotene; Beverages; Biomarkers, Tumor; Carotenoids; Cell Death; Cell Proliferation; Cell Transformation, Neoplastic; Colonic Neoplasms; Cross-Over Studies; Daucus carota; Feces; Humans; Lycopene; Male; Solanum lycopersicum; Tumor Cells, Cultured; Water

One trial reported beta-carotene supplementation was protective of adenomatous polyp recurrence in nonsmokers. We now examine the relation of serum and dietary carotenoids and vitamin A to adenomatous polyp recurrence in a subcohort of 834 participants in a low fat, high fiber, high fruit and vegetable dietary intervention, the Polyp Prevention Trial. Multivariate odds ratio (OR) and 95% confidence intervals (CI) of polyp recurrence were obtained using baseline or the average (first 3 years of the trial) carotenoid and vitamin A values after adjustment for covariates. Compared to the lowest quartile of baseline alpha-carotene concentrations, the OR of multiple polyp recurrence for the highest quartile was 0.55 (95% CI = 0.30-0.99) and the OR of right-sided recurrence was 0.60 (95% CI = 0.37-0.95). Baseline dietary intakes of alpha-carotene and vitamin A from food with/without supplements were inversely associated with any recurrence (p for linear trend = 0.03-alpha-carotene; p = 0.004 and p = 0.007 -intakes of vitamin A). Compared to the lowest quartile of averaged beta-carotene concentrations, the OR of multiple adenomas for the highest quartile was 0.40 (95% CI = 0.22-0.75) with an inverse trend (p = 0.02). The risk was inversely related to averaged: alpha-carotene concentrations and right-sided polyps; alpha-carotene intake and recurrence of any, multiple and right-sided polyps; beta-carotene intake and multiple adenoma recurrence; vitamin A from food (with supplements) and each adverse endpoint. Thus, alpha-carotene and vitamin A may protect against recurrence in nonsmokers and nondrinkers or be indicative of compliance or another healthy lifestyle factor that reduces risk.

Topics: Adenomatous Polyps; Aged; Alcohol Drinking; Antioxidants; beta Carotene; Carotenoids; Colonic Neoplasms; Diet; Female; Humans; Life Style; Male; Middle Aged; Neoplasm Recurrence, Local; Odds Ratio; Patient Compliance; Risk Factors; Smoking

The aims of the present study were: (1) to determine whether short-term supplementation of beta-carotene (BC) or vitamin E (VE; alpha-tocopherol) would result in their respective accumulation in normal colonic mucosa and in adenomatous polyps; (2) to determine whether the intake of BC would interfere with the concentration of VE in these target tissues.. Blood and colonic biopsy samples were taken before and after supplementation.. Eighteen volunteers with colonic adenomatous polyps were enrolled into this study.. The supplementation lasted for 43 days and patients were examined over the whole period. Subjects were randomised into four groups according to the four different supplementations: placebo, natural BC (25 000 IU/day), natural VE (400 IU/day), combination BC/VE.. Initially we were aiming for recruitment of 20 patients in each group, however after 2 y of study (1997-1999), we terminated the study because of slow recruitment and analysed the data. In placebo subjects after supplementation, the plasma concentrations of BC and VE remained unchanged, however only two patients were recruited in this group and therefore we did not include this group in our final analysis. In BC group, the plasma BC concentrations increased significantly (P<0.001), while VE concentrations were unchanged. In VE group, VE concentrations increased (P<0.01) and BC did not change, and in BC/VE group both BC (P<0.001) and VE levels (P<0.01) increased significantly. After supplementation, the tissue concentration of BC in normal colonic mucosa in BC group increased significantly (P<0.01) while the VE concentration did not change. In VE group, the concentration of VE in normal colonic mucosa increased slightly but did not reach statistical significance. However, VE concentration increased significantly (P<0.05) in the polyps of this group. In BC/VE group, in which patients received the combination treatment, the BC concentration of normal colonic mucosa increased (P<0.05) but, surprisingly, the VE concentration decreased significantly (P<0.01). Interestingly in the polyps, although the BC concentration increased (P<0.01), the concentration of VE was reduced moderately but did not reach statistical significance.. Supplementation of BC in doses used in this study may have significantly interfered with the VE concentration in the examined tissue and probably with its metabolic pathway.

Topics: Adenomatous Polyps; Adult; Aged; alpha-Tocopherol; Antioxidants; beta Carotene; Biopsy; Colon; Colonic Neoplasms; Dietary Supplements; Drug Interactions; Female; Humans; Intestinal Mucosa; Male; Middle Aged; Tissue Distribution

The Physicians' Health Study (PHS) was a randomized trial of beta-carotene (50 mg, alternate days) and aspirin in primary prevention of cancer and cardiovascular disease among 22,071 US male physicians. This report updates results for beta-carotene and examines effect modification by baseline characteristics.. Beta-carotene's effect on cancer over nearly 13 years was examined overall and within subgroups defined by baseline characteristics using proportional-hazards models.. 2667 incident cancers were confirmed, with 1117 prostate, 267 colon, and 178 lung cancers. There were no significant differences with supplementation in total (relative risk (RR) = 1.0, 95% confidence interval (CI) = 0.9-1.0); prostate (RR = 1.0, 95% CI = 0.9-1.1); colon (RR = 0.9, 95% CI = 0.7-1.2); or lung (RR = 0.9, 95% CI = 0.7-1.2) cancer, and no differences over time. In subgroup analyses, total cancer was modestly reduced with supplementation among those aged 70+ years (RR = 0.8, 95% CI = 0.7-1.0), daily drinkers of alcohol (RR = 0.9, 95% CI = 0.8-1.0), and those in the highest BMI quartile (RR = 0.9, 95% CI = 0.7-1.0). Prostate cancer was reduced with supplementation among those in the highest BMI quartile (RR = 0.8, 95% CI = 0.6-1.0), and colon cancer was reduced among daily drinkers of alcohol (RR = 0.5, 95% CI = 0.3-0.8).. The PHS found no overall effect of beta-carotene on total cancer, or the three most common site-specific cancers. The possibility of risk reduction within specific subgroups remains.

Topics: Adult; Aged; Aged, 80 and over; Aspirin; beta Carotene; Body Mass Index; Cardiovascular Diseases; Colonic Neoplasms; Double-Blind Method; Humans; Incidence; Life Style; Lung Neoplasms; Male; Middle Aged; Neoplasms; Physicians; Prostatic Neoplasms; Risk Factors; United States

The Physicians' Health Study was a randomized, double-blind, placebo-controlled trial using a 2x2 factorial design including supplementation with beta-carotene (50 mg every other day) in the primary prevention of cancer among 22,071 U.S. male physicians ages 40-84 years at randomization. Before randomization, the authors collected baseline blood specimens to determine whether any benefit was greater among or confined to those with low baseline levels of beta-carotene.. Baseline blood samples were collected from 14,916 participants. These samples were assayed, according to a nested case-control design, from 1439 men subsequently diagnosed with cancer over 12 years of follow-up (631 with prostate carcinoma) and 2204 controls matched by age and smoking habits.. Men in the lowest quartile for plasma beta-carotene at baseline had a marginally significant (P = 0.07) increased risk of cancer compared with those in the highest quartile (relative risk [RR] = 1.30, 95% confidence interval [CI], 0.98-1.74). Men in the lowest quartile assigned at random to beta-carotene supplementation had a possible but nonsignificant decrease in overall cancer risk (RR = 0.83, 95% CI, 0.63-1.09) compared with those assigned to placebo. This was primarily due to a significant reduction in the risk of prostate carcinoma (RR = 0.68, 95% CI, 0. 46-0.99) in this group. After the first 2 years of follow-up were excluded, the results were virtually unchanged.. These prespecified subgroup analyses appeared to support the idea that beta-carotene supplementation may reduce risk of prostate carcinoma among those with low baseline levels. Further follow-up of this population will help determine whether these findings are valid.

Topics: Adult; Aged; Aged, 80 and over; beta Carotene; Case-Control Studies; Colonic Neoplasms; Dietary Supplements; Double-Blind Method; Epidemiologic Studies; Follow-Up Studies; Humans; Lung Neoplasms; Lymphoma; Male; Melanoma; Middle Aged; Prostatic Neoplasms; Risk; Smoking

Results from a number of studies suggest that beta-carotene-containing foods prevent the initiation or progression of various cancers. One possible mechanism for this effect could be enhancement of the immune response. The aim of this study was to determine whether beta-carotene modulates T lymphocyte subsets in patients affected with colonic polyps or cancerous lesions. Patients with previous adenomatous colonic polyps (n = 18) or colon cancers (n = 19) were randomized to receive placebo or beta-carotene (30 mg/day) for three months. Percentages of T lymphocyte subsets were determined using flow cytometry in blood samples collected before randomization and at three months. T lymphocyte subsets of 14 normal control subjects were also determined for comparison. Initially, there was no difference in total leukocyte counts, percentage of lymphocytes, and various subsets of lymphocytes among the three groups, although in cancer patients there was a lower percentage of CD4 and interleukin-2 (IL-2) receptor-positive (IL-2R+) cells than in patients with polyps and in controls. After supplementation with beta-carotene, a significant increase in IL-2R+ T lymphocytes (from 12.7 +/- 3.0% to 26.0 +/- 1.9%) and CD4+ lymphocytes (from 40.9 +/- 3.1% to 45.6 +/- 3.2%) was seen only in the cancer patients. These percentages remained unchanged in patients with adenomatous polyps receiving placebo or beta-carotene. We concluded that beta-carotene increased the number of IL-2R+ T lymphocytes and CD4+ lymphocytes, which in turn may produce IL-2 only in patients with cancer who may already have some deficiency in their immune system. This increase in activated T lymphocytes may mediate cytotoxic reactions to cancer cells via cytokine production.

Topics: Adult; Antioxidants; beta Carotene; Cohort Studies; Colonic Neoplasms; Colonic Polyps; Female; Flow Cytometry; Humans; Male; Middle Aged; Reference Values; T-Lymphocyte Subsets; Time Factors; Tretinoin; Vitamin A; Vitamin E

Epidemiologic studies have shown that consuming foods containing beta-carotene is associated with a decreased incidence of colon cancer. The validity of this association has recently been questioned. It is not known if the rate of colonic cell proliferation differs among individuals with or without a history of colonic polyps or cancer and if proliferation changes in response to beta-carotene.. This study was intended to (a) determine whether differences exist in colonic cell proliferation in individuals with and without prior colonic polyps or tumors, (b) demonstrate that beta-carotene accumulates in colonic mucosa following dietary supplementation, and (c) determine whether mucosal beta-carotene accumulation influences colonic cell proliferation.. Subjects were enrolled in the phase I study from June 1991 until February 1994. The participants included 20 individuals (11 males and nine females, aged 62.3 +/- 8.9 years [means +/- SD]) with normal colons (as judged by recent colonoscopy), 40 (24 males and 16 females, aged 59.6 +/- 10.1 years) with a history of colonic polyp(s), and 41 (30 males and 11 females, aged 67.2 +/- 9.7 years) with prior colon cancer. The subjects in the last two groups consumed either 30 mg of beta-carotene or placebo each morning for 3 months. This dose of beta-carotene has no known toxic effects, but it can increase the serum level by approximately 10-fold. beta-carotene concentration in serum and colonic tissue was quantitated by high-pressure liquid chromatography in samples collected before and after supplementation with beta-carotene or placebo. Cellular proliferation was assessed on the basis of tissue ornithine decarboxylase activity, urinary polyamine excretion, and proliferating cell nuclear antigen expression. The differences in colonic cell proliferation parameters due to beta-carotene supplementation, within and among different groups, were evaluated by the Wilcoxon matched-pairs signed ranked test and the Mann-Whitney test, respectively. All statistical tests were two-sided.. Colonic cell proliferation did not differ in samples obtained from individuals with and without prior colonic polyp(s) or cancer. beta-carotene concentrations in serum and colonic tissue were significantly increased in groups receiving beta-carotene (P < .001). However, cell proliferation did not differ, as judged by any of the three measures, among samples from all experimental groups collected before and after supplementation with beta-carotene.. Dietary supplementation with beta-carotene for a period of 3 months does not alter colonic cell proliferation in individuals with a history of colonic polyps or cancer.. The mechanism by which beta-carotene might reduce colon cancer incidence does not appear to involve or result in a change in cell proliferation in the normal colonic mucosa as studied in individuals with a history of colonic polyps or cancer.

Topics: Adult; Aged; Aged, 80 and over; beta Carotene; Carotenoids; Cell Division; Colon; Colonic Neoplasms; Colonic Polyps; Female; Humans; Male; Middle Aged; Ornithine Decarboxylase; Proliferating Cell Nuclear Antigen

To determine whether patients with colon cancer metabolize beta-carotene differently from benign colon polyp patients, a normal control group (n = 13) and groups of resected colon polyp patients (n = 29) or resected colon cancer patients (Dukes A and B1, n = 21) were supplemented with placebo or beta-carotene (30 mg/day) taken with their morning meals for three months. Serum samples at zero and three months of the study were analyzed blindly for retinoic acid and beta-carotene. The results showed that beta-carotene levels in the serum of colon polyp and colon cancer groups were 8- to 12-fold higher than in the untreated control or the placebo-treated groups. The benign polyp subjects (n = 17) receiving beta-carotene showed a significant rise in serum trans-retinoic acid at three months compared with Time 0. The trans-retinoic acid values from the colon cancer group receiving beta-carotene (n = 11) or placebo (n = 10) were significantly lower than the values from the beta-carotene-supplemented colon polyp group. It appears that trans-retinoic acid levels in response to beta-carotene supplementation are different between treated cancer and benign patients because of different body demands for retinoic acid.

Topics: Adult; Aged; Aged, 80 and over; beta Carotene; Carotenoids; Colonic Neoplasms; Colonic Polyps; Female; Humans; Kinetics; Male; Middle Aged; Tretinoin

The aim of this study was to evaluate the colonic mucosal beta-carotene (BC) concentration following supplementation with BC and to determine if an increase in BC concentration influences vitamin E (alpha-tocopherol) status. The concentration of BC and alpha-tocopherol was assessed in serum and colonic tissue obtained from subjects with a history of colonic polyps or resected cancer (Dukes A, B1, or B2). Serum and mucosal biopsy samples were obtained prior to and following 3 months daily p.o. supplementation with 30 mg of BC or placebo. The concentration of BC was significantly increased in serum and colonic mucosa from both polyp and cancer subjects following supplementation as compared to presupplementation values and values from subjects receiving a placebo. The concentration of alpha-tocopherol in serum from cancer subjects was significantly decreased in samples obtained at the end of 3 months of BC supplementation as compared to placebo-matched controls. In BC-supplemented polyp subjects the tissue concentration of alpha-tocopherol was also significantly decreased relative to presupplementation values. The results indicate that BC supplementation does result in a significant accumulation of BC in the colonic mucosa but that the alpha-tocopherol concentration in both serum and colonic tissue may be compromised by an increased intake of BC. The mechanism for the decrease in alpha-tocopherol in conjunction with the increase in BC will require further study in order to develop strategies which will prevent vitamin E deficiency in BC-supplemented individuals.

Topics: Adult; Aged; Aged, 80 and over; beta Carotene; Carotenoids; Colon; Colonic Neoplasms; Colonic Polyps; Female; Follow-Up Studies; Humans; Intestinal Mucosa; Male; Middle Aged; Placebos; Single-Blind Method; Vitamin A; Vitamin E; Vitamin E Deficiency

Cancer cachexia is a metabolic disease affecting multiple organs and characterized by loss adipose and muscle tissues. Metabolic dysregulated of adipose tissue has a crucial role in cancer cachexia. β-Carotene (BC) is stored in adipose tissues and increases muscle mass and differentiation. However, its regulatory effects on adipose tissues in cancer cachexia have not been investigated yet. In this study, we found that BC supplementations could inhibit several cancer cachexia-related changes, including decreased carcass-tumor (carcass weight after tumor removal), adipose weights, and muscle weights in CT26-induced cancer cachexia mice. Moreover, BC supplementations suppressed cancer cachexia-induced lipolysis, fat browning, hepatic gluconeogenesis, and systemic inflammation. Altered diversity and composition of gut microbiota in cancer cachexia were restored by the BC supplementations. BC treatments could reverse the down-regulated adipogenesis and dysregulated mitochondrial respiration and glycolysis in adipocytes and colon cancer organoid co-culture systems. Taken together, these results suggest that BC can be a potential therapeutic strategy for cancer cachexia.

Topics: Adipose Tissue; Animals; beta Carotene; Cachexia; Colonic Neoplasms; Gastrointestinal Microbiome; Mice; Muscle, Skeletal; Neoplasms

Cyclins and cyclin-dependent kinases (CDKs) regulate the cell cycle, which is important for cell proliferation and development. Cyclins bind to and activate CDKs, which then drive the cell cycle. The expression of cyclins periodically changes throughout the cell cycle, while that of CDKs remains constant. To elucidate the mechanisms underlying the constant expression of CDKs, we search for compounds that alter their expression and discover that the natural product fucoxanthinol downregulates CDK2, 4, and 6 expression. We then develop a method to immobilize a compound with a hydroxyl group onto FG beads

Topics: beta Carotene; Biological Products; Colonic Neoplasms; Cyclin-Dependent Kinase 2; Cyclin-Dependent Kinase 4; Cyclin-Dependent Kinase 6; Cyclins; Humans; Ribosomal Proteins

The tumor microenvironment (TME), consisting of stromal fibroblasts, immune cells, cancer cells and other cell types, plays a crucial role in cancer progression and metastasis. M2 macrophages and activated fibroblasts (AFs) modulate behavior of cancer cells in the TME. Since nutritional effects on cancer progression, including colorectal cancer (CRC), may be mediated by alterations in the TME, we determined the ability of β-carotene (BC) to mediate anti-cancer effects through regulation of macrophage polarization and fibroblast activation in CRC. The M2 macrophage phenotype was induced by treating U937 cells with phorbol-12-myristate-13-acetate and interleukin (IL)-4. Treatment of these M2 macrophages with BC led to suppression of M2-type macrophage-associated markers and of the IL-6/STAT3 signaling pathway. In separate experiments, AFs were induced by treating CCD-18Co cells with transforming growth factor-β1. BC treatment suppressed expression of fibroblast activation markers. In addition, conditioned media from BC-treated M2 macrophages and AF inhibited cancer stem cell markers, colon cancer cell invasiveness and migration, and the epithelial-mesenchymal transition (EMT). In vivo, BC supplementation inhibited tumor formation and the expression of M2 macrophage markers in an azoxymethane/dextran sodium sulfate-induced colitis-associated CRC mouse model. To our knowledge, the present findings provide the first evidence suggesting that the potential therapeutic effects of BC on CRC are mediated by the inhibition of M2 macrophage polarization and fibroblast activation.

Topics: Animals; Antineoplastic Agents; beta Carotene; Cell Movement; Cell Proliferation; Colonic Neoplasms; Epithelial-Mesenchymal Transition; Female; Fibroblasts; HCT116 Cells; Humans; Interleukin-6; Macrophages; Male; Mice; Mice, Inbred BALB C; Neoplasm Invasiveness; Neoplastic Stem Cells; Signal Transduction; STAT3 Transcription Factor; Tumor Microenvironment; U937 Cells

P-glycoprotein (P-gp or MDR1) is an ATP-binding cassette (ABC) transporter. It is involved in the efflux of several anticancer drugs, which leads to chemotherapy failure and multidrug resistance (MDR) in cancer cells. Representative secondary metabolites (SM) including phenolics (EGCG and thymol), terpenoids (menthol, aromadendrene, β-sitosterol-O-glucoside, and β-carotene), and alkaloids (glaucine, harmine, and sanguinarine) were evaluated as potential P-gp inhibitors (transporter activity and expression level) in P-gp expressing Caco-2 and CEM/ADR5000 cancer cell lines. Selected SM increased the accumulation of the rhodamine 123 (Rho123) and calcein-AM (CAM) in a dose dependent manner in Caco-2 cells, indicating that they act as competitive inhibitors of P-gp. Non-toxic concentrations of β-carotene (40μM) and sanguinarine (1μM) significantly inhibited Rho123 and CAM efflux in CEM/ADR5000 cells by 222.42% and 259.25% and by 244.02% and 290.16%, respectively relative to verapamil (100%). Combination of the saponin digitonin (5μM), which also inhibits P-gp, with SM significantly enhanced the inhibition of P-gp activity. The results were correlated with the data obtained from a quantitative analysis of MDR1 expression. Both compounds significantly decreased mRNA levels of the MDR1 gene to 48% (p<0.01) and 46% (p<0.01) in Caco-2, and to 61% (p<0.05) and 1% (p<0.001) in CEM/ADR5000 cells, respectively as compared to the untreated control (100%). Combinations of digitonin with SM resulted in a significant down-regulation of MDR1. Our findings provide evidence that the selected SM interfere directly and/or indirectly with P-gp function. Combinations of different P-gp substrates, such as digitonin alone and together with the set of SM, can mediate MDR reversal in cancer cells.

Topics: Alkaloids; Antineoplastic Agents, Phytogenic; ATP Binding Cassette Transporter, Subfamily B, Member 1; Benzophenanthridines; beta Carotene; Caco-2 Cells; Colonic Neoplasms; Digitonin; Dose-Response Relationship, Drug; Drug Combinations; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Drug Synergism; Fluoresceins; Humans; Isoquinolines; Leukemia; Phenols; Phytochemicals; Phytotherapy; Plant Extracts; Rhodamine 123; RNA, Messenger; Terpenes

Previous cohort studies examining the association of serum antioxidant levels and risk of colorectal cancer have used a single (baseline) measurement only. In the present study, we assessed the association of serum levels of eight antioxidant nutrients in relation to risk of colorectal cancer, using repeated measurements.. Data on a subsample of women in the Women's Health Initiative with repeated measurements of serum retinol, α-carotene, β-carotene, β-cryptoxanthin, lutein+zeaxanthin, lycopene, α-tocopherol and γ-tocopherol during follow-up were included in the analysis. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CIs).. Among 5477 women with baseline serum antioxidant values, 88 incident cases of colorectal cancer were identified over a median follow-up time of 12 years. Serum antioxidants measured at baseline generally showed no association with risk of colorectal cancer, although serum β-carotene at baseline showed a non-significant inverse association with colon cancer alone. Furthermore, using the repeated measurements of β-carotene, the average of all measurements was inversely associated with risk of both colorectal and colon cancer: HRs for highest vs lowest tertile 0.54, 95% CI 0.31-0.96, and 0.47, 95% CI 0.25-0.88, respectively. No associations were seen with other antioxidant nutrients in the repeated measure analyses.. In this study, baseline levels of antioxidant nutrients were not associated with risk of colorectal or colon cancer; however, using repeated measures, a relatively high serum level of β-carotene (average of all measurements) was inversely associated with risk of colon and colorectal cancer in postmenopausal women.

Topics: Aged; Antioxidants; beta Carotene; Carotenoids; Colonic Neoplasms; Colorectal Neoplasms; Female; Humans; Incidence; Middle Aged; Nutrition Assessment; Nutritional Status; Proportional Hazards Models; Risk Factors; Tocopherols; Vitamin A; Women's Health

Lycopene beta-cyclase (tlcy-b) tomatoes, obtained by modulating carotenogenesis via genetic engineering, contain a large amount of beta-carotene, as clearly visible by their intense orange colour. In the present study we have subjected tlcy-b tomatoes to an in vitro simulated digestion and analysed the effects of digestate on cell proliferation. To this aim we used HT-29 human colon adenocarcinoma cells, grown in monolayers, as a model. Digested tomatoes were diluted (20 ml, 50 ml and 100 ml/l) in culture medium and added to the cells for different incubation times (24 h, 48 h and 72 h). Inhibition of cell growth by tomato digestate was dose-dependent and resulted from an arrest of cell cycle progression at the G0/G1 and G2/M phase and by apoptosis induction. A down-regulation of cyclin D1, Bcl-2 and Bcl-xl expression was observed. We also found that heat treatment of samples before digestion enhanced beta-carotene release and therefore cell growth inhibition. To induce with purified beta-carotene solubilised in tetrahydrofuran the same cell growth inhibition obtained with the tomato digestate, a higher amount of the carotenoid was necessary, suggesting that beta-carotene micellarised during digestion is utilised more efficiently by the cells, but also that other tomato molecules, reasonably made available during digestion, may be present and cooperate with beta-carotene in promoting cell growth arrest.

Topics: Adenocarcinoma; Analysis of Variance; Animals; Apoptosis; bcl-X Protein; beta Carotene; Biomarkers; Caspase 3; Colonic Neoplasms; Cyclin D1; Digestion; Down-Regulation; Genes, bcl-2; Genetic Markers; HT29 Cells; Humans; Interphase; Intramolecular Lyases; Plants, Genetically Modified; Solanum lycopersicum; Swine

Although several mechanisms have been proposed to explain the putative role of beta-carotene in cancer, no studies have investigated a possible influence of beta-carotene on caveolin-1 (cav-1) pathway, an important intracellular signaling deregulated in cancer. Here, different human colon and prostate cancer cell lines, expressing (HCT-116, PC-3 cells) or not (Caco-2, LNCaP cells) cav-1, were treated with varying concentrations of beta-carotene (0.5-30 muM) for different periods of time (3-72 h) and the effects on cell growth were investigated. The results of this study show that (i) beta-carotene acted as a growth-inhibitory agent in cav-1-positive cells, but not in cav-1-negative cells; (ii) in cav-1-positive cells, the carotenoid downregulated in a dose- and time-dependent manner the expression of cav-1 protein and messenger RNA levels and inhibited AKT phosphorylation which, in turn, stimulated apoptosis by increasing the expression of beta-catenin and c-myc and the activity of caspases-3, -7, -8 and -9; when the carotenoid was removed from culture medium, a progressive increase in cell growth was observed with respect to beta-carotene-treated cells and (iii) the transfection of cav-1 in cav-1-negative cells increased cell sensitivity to beta-carotene by inducing apoptosis. This effect was accompanied by a reduction of both cav-1 and AKT phosphorylation and by an increase of c-myc and beta-catenin expression. Silencing of c-Myc attenuated beta-carotene-induced apoptosis and beta-catenin expression. All together, these data suggest that the modulation of cav-1 pathway by beta-carotene could be a novel mechanism by which the carotenoid acts as a potent growth-inhibitory agent in cancer cells.

Topics: Apoptosis; Base Sequence; beta Carotene; beta Catenin; Caveolin 1; Cell Division; Cell Line, Tumor; Colonic Neoplasms; DNA Primers; Fluorescent Antibody Technique; Gene Silencing; Genes, myc; Humans; Immunohistochemistry; In Situ Nick-End Labeling; Male; Phosphorylation; Prostatic Neoplasms; Reverse Transcriptase Polymerase Chain Reaction

Zeaxanthin (Zea) and lutein are the only dietary carotenoids that accumulate in the macular region of the retina and lens. It was proposed that these carotenoids protect these tissues against photooxidative damage. Few plant foods are enriched in Zea, and information about the bioavailability of Zea from these foods and its accumulation in ocular tissues is limited. The amounts of free Zea and its mono- and diesters were measured for several plant foods that have relatively high concentrations of this xanthophyll. Wolfberry had the greatest concentration of Zea with a diester that accounts for 95% of the total. Free, mono-, and diesters of Zea were present in orange and red peppers, whereas only Zea monoesters were detected in squash. Zea esters were partially hydrolyzed by carboxyl ester lipase (CEL) during simulated digestion. The efficiency of micellarization was dependent on speciation with combined means of free Zea, Zea monoesters, Zea diesters from the digested foods of 81 +/- 8, 44 +/- 5, and 11 +/- 4%, respectively. When exposed to micelles generated during digestion of the test foods, Zea uptake by Caco-2 cells was proportional to the medium content (11-14%). Free Zea was the most abundant form in Caco-2 cells, although Zea monoesters also were detected (<8 +/- 0.7% vs. free Zea). CEL enhanced Zea uptake from micelles (12.3-fold; P < 0.05) by hydrolyzing Zea esters. After cell uptake, concentrations of free and monoesterified Zea remained relatively stable. These data suggest that dietary Zea esters are hydrolyzed by CEL during the small intestinal phase of digestion and that this conversion enhances Zea bioavailability.

Topics: beta Carotene; Biological Transport; Carboxylesterase; Cell Line, Tumor; Colonic Neoplasms; Digestion; Food Analysis; Humans; Hydrolysis; Micelles; Palmitates; Xanthophylls; Zeaxanthins

Chronic inflammation in gastrointestinal tract has been suggested as a risk factor for tumor formation. The effect of dietary supplementation of quercetin or beta-carotene on colon carcinogenesis and inflammatory response in rats fed with high-fat diet rich in omega-6 fatty acids was assessed. Animals were exposed to two weekly subcutaneous injections of AOM (azoxymethane) at a single dose of 15 mg/kg body weight. A portion of rats from each group was sacrificed at 8 weeks after the last AOM treatment to determine ACF (aberrant crypt foci) formation. Colonic mucosa expression of iNOS (inducible nitric oxide) and COX-2 (cyclooxygenase-2) protein, and blood PGE2 (prostaglandin E2) level were measured. The remaining groups of animals were sacrificed at 33 weeks after the last AOM treatment to examine colon tumor formation. Rats on high-fat diet developed more aberrant crypt foci (P<0.05) compared with those of rats on regular diet. In the same vein, but in contrast to the effect seen with regular diet, the high-fat diet induced a significant up-regulation of iNOS expression. There was no significant change in the extent of COX-2 expression or in the PGE2 levels. Quercetin or beta-carotene supplementation reduced the number of ACF only in animals fed high-fat diet (p<0.05), however, no significant difference in tumor incidence was found. At week 33, the expression of iNOS was reduced by quercetin without a statistical significance, and COX-2 expression was slightly reduced in rats on beta-carotene supplementation. No change in PGE2 levels was observed. Whilst dietary antioxidants are considered as effective suppressors for precancerous lesion formation in colons exposed to high-risk diet, it is clear that elucidating the role of individual antioxidants in colon tumor formation coupled with an understanding of the molecular mechanisms involved would benefit colon cancer prevention strategies.

Topics: Animals; Azoxymethane; beta Carotene; Carcinogens; Colonic Neoplasms; Cyclooxygenase 2; Dietary Fats; Fatty Acids, Omega-6; Male; Models, Biological; Nitric Oxide Synthase Type II; Quercetin; Rats; Rats, Sprague-Dawley; Vitamins

Epidemiological studies suggest that carotenoids such as beta-carotene and lutein play an important role in reducing the risk for several cancers. However, in colon cancer there is ambiguity with regard to the role of these compounds in that both preventive effects and tumor promotion have been observed. In the present study we observed that male F344 rats were able to tolerate up to 2,500 ppm of beta-carotene as well as of lutein. We have then assessed the chemopreventive efficacy of beta-carotene and lutein at dose levels of approximately 4 and 8% of the 2,500 ppm tolerated dose (TD) and also approximately 40 and 80% of the TD on azoxymethane (AOM)-induced colon carcinogenesis, using aberrant crypt foci (ACF) as a surrogate biomarker for colon cancer. Throughout the experiments, 5-week-old male F344 rats were fed the control diet (modified AIN-76A) or experimental diets containing 100 or 200 ppm (approximately 4 or 8% of the 2,500 ppm TD), or 1,000 or 2,000 ppm ( approximately 40 or 80% of the 2,500 ppm TD) of beta-carotene and lutein (n=10 rats/group). After 2 weeks on the experimental or control diets, all animals were injected with AOM (15 mg/kg body wt., once weekly for 2 weeks). At 14 weeks of age, all rats were killed, and their colons were evaluated for ACF. Administration of 100 or 200 ppm of beta-carotene inhibited AOM-induced total colonic ACF formation by 24% (p<0.01) and 36% (p<0.001), respectively, whereas lutein at 200 ppm produced a 27% inhibition (p<0.01) yet had no significant effect at the 100 ppm dose level. Surprisingly, administration of 1,000 or 2,000 ppm of beta-carotene and lutein increased colonic ACF formation in a dose-dependent manner, i.e., to 124% and 144% for the former and 110% and 159% for the latter. These results clearly suggest that further studies are warranted to determine whether the increase in ACF incidence by high doses of beta-carotene and lutein will also lead to an increase in tumor outcome. Taken together these data indicate that the chemopreventive activity of beta-carotene and lutein against colon carcinogenesis depends on the dose level.

Topics: Animals; Antioxidants; Azoxymethane; beta Carotene; Carcinogens; Chemoprevention; Colonic Neoplasms; Diet; Dose-Response Relationship, Drug; Lutein; Male; Precancerous Conditions; Rats; Rats, Inbred F344

Experimental studies have shown that beta-carotene inhibited the growth of colon cancer cells, and human trials have demonstrated that the carotenoid reduces colon cell proliferation of adenomatous polyps; however, molecular mechanisms underlying this chemopreventive activity remain unclear. Because COX-2 has been implicated as a causative factor in colon carcinogenesis, the present study was designed to investigate the relation between the growth-inhibitory effect of the carotenoid and COX-2 expression in colon cancer cells. We evaluated the effects of beta-carotene on the growth of human colon adenocarcinoma cells overexpressing (LS-174, HT-29, WiDr) or not expressing (HCT116) COX-2. We also studied COX-2 expression induced by heregulin-alpha, apoptosis induction, reactive oxygen species (ROS) production, and extracellular signal-regulated kinase 1/2 (ERK1/2) activation. beta-Carotene (0.5-2.0 micromol/L) decreased COX-2 expression (P < 0.05) and prostaglandin E(2) (PGE(2)) production (P < 0.05) in colon cancer cells. This effect was not observed in cells treated with retinoic acid or retinol. The downregulation of COX-2 by the carotenoid occurred in both untreated and heregulin-treated cells. It was accompanied by an increased ability of cells to undergo apoptosis and by a decrease in intracellular ROS production and in the activation of ERK1/2. Moreover, cells not expressing COX-2 were insensitive to the growth-inhibitory and proapoptotic effects of the carotenoid. Here, we report that the suppression of COX-2 by beta-carotene may represent a molecular mechanism by which this compound acts as an antitumor agent in colon carcinogenesis.

Topics: beta Carotene; Caspase 3; Caspases; Cell Cycle; Cell Line, Tumor; Colonic Neoplasms; Cyclooxygenase 1; Cyclooxygenase 2; Dinoprostone; Extracellular Signal-Regulated MAP Kinases; Humans; Isoenzymes; Membrane Proteins; Neuregulin-1; Prostaglandin-Endoperoxide Synthases; Reactive Oxygen Species

Microsatellite instability (MSI) is one form of genomic instability that occurs in 10% to 20% of sporadic colon tumors and almost all hereditary nonpolyposis colon cancers. However, little is known about how environmental factors (e.g., diet) may influence MSI in sporadic colon cancer.. We used data from a population-based case-control study in North Carolina (486 colon cancer cases and 1,048 controls) to examine associations of diet (total energy, macronutrients, micronutrients, and food groups) with MSI. In-person interviews elicited information on potential colon cancer risk factors, and a previously validated food frequency questionnaire adapted to include regional foods was used to assess diet over the year before diagnosis or interview date. MSI was classified as MSI-high (MSI-H) and MSI-low or microsatellite stable (MSI-L/MSS). Multivariate logistic regression models estimated energy-adjusted and non-energy-adjusted odds ratios (OR).. Ten percent of the cases (n = 49) had MSI-H tumors (29% African American). The strongest associations between diet and MSI were observed in case-control comparisons: there was a robust inverse association between MSI-H status and beta-carotene [OR, 0.4; 95% confidence interval (95% CI), 0.2-0.9] and positive associations with energy-adjusted refined carbohydrates (OR, 2.2; 95% CI, 0.9-5.4) and non-energy-adjusted read meat intake (OR, 2.0; 95% CI, 0.9-4.2). Compared with controls, MSI-L/MSS tumors were statistically significantly associated with energy-adjusted vitamin C, vitamin E, calcium, dietary fiber, and dark green vegetables and positively associated with total energy intake (all Ps for trend < 0.05). In case-case comparisons, no dietary factors were significantly differently related to MSI-H compared with MSI-L/MSS tumors.. Refined carbohydrate and red meat consumption may promote development of MSI-H tumors, whereas beta-carotene may be associated with lower risk.

Topics: Adult; Aged; beta Carotene; Black People; Case-Control Studies; Colonic Neoplasms; Diet; Diet Surveys; Dietary Carbohydrates; Female; Genomic Instability; Humans; Life Style; Logistic Models; Male; Meat; Microsatellite Repeats; Middle Aged; North Carolina; Risk Factors; White People

Some epidemiological studies suggest that consumption of fruits and vegetables with a high carotenoid content may protect against colon cancer (CC). The evidence, however, is not completely consistent. Given the inconsistencies in findings in previous studies and continued interest in identifying modifiable risk factors for CC, a case-control study of French-Canadian in Montreal, Canada, was undertaken to examine the possible association between dietary carotenoids and CC risk and to investigate whether this association varies in relation to lifestyle factors such as smoking or diet, and particularly the high consumption of long-chain polyunsaturated fatty acids (LCPUFA). A total of 402 colorectal cases (200 males and 202 females) and 688 population-based controls matched for age, gender and place of residence were interviewed. Dietary intake was assessed through a validated food frequency questionnaire that collected information on over 200 food items and recipes. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated in unconditional logistic regression models. After adjustment for important variables such as total energy intake, no association was found between dietary intake of carotenoids and CC risk. For women with high intakes of LCPUFA, an inverse association was found between lutein + zeaxanthin and CC risk. ORs were 0.41; 95%CI (0.19-0.91), p=0.03 for eicosapentaenoic acid, and OR=0.36, 95%CI (0.19-0.78), p=0.01 for docosahexaenoic acid, when the upper quartiles of intake were compared to the lower. Among never-smokers, a significantly reduced risk of CC was associated with intake of beta-carotene [OR=0.44, 95%CI (0.21-0.92) and p=0.02], whereas an inverse association was found between lycopene intake and CC risk [OR=0.63, 95%CI (0.40-0.98) and p=0.05] among smokers. The results of our study suggest that a diet rich in both lutein + zeaxanthin and LCPUFAs may help prevent CC in French-Canadian females.

Topics: Adult; Aged; beta Carotene; Carotenoids; Case-Control Studies; Colonic Neoplasms; Docosahexaenoic Acids; Eicosapentaenoic Acid; Fatty Acids, Unsaturated; Female; Humans; Lutein; Male; Middle Aged; Xanthophylls; Zeaxanthins

We demonstrated previously that beta-carotene may affect cell growth by a redox mechanism. The purpose of this study was to determine whether the redox-sensitive transcription factor nuclear factor (NF)-kappaB may be involved in the growth-inhibitory and proapoptotic effects of the carotenoid. To test this hypothesis, human leukemic cells (HL-60) and colon adenocarcinoma cells (LS-174 and WiDr) were treated with beta-carotene, alone or in combination with alpha-tocopherol or N-acetylcysteine, and changes in 1) cell oxidative status, 2) cell growth and apoptosis, 3) DNA-binding activity of NF-kappaB and 4) expression of c-myc, a NF-kappaB target gene involved in apoptosis, were evaluated. In HL-60 cells, beta-carotene induced a significant increase in reactive oxygen species (ROS) production (P < 0.001) and in oxidized glutathione (GSSG) content (P < 0.005) at concentrations >/=10 micro mol/L. These effects were always accompanied by a sustained elevation of NF-kappaB and by a significant inhibition (P < 0.002) of cell growth. NF-kappaB DNA-binding activity increased at 3 h and persisted for at least 48 h. Colon adenocarcinoma cells displayed substantial differences in their sensitivity to beta-carotene, exhibiting increased ROS levels and activation of NF-kappaB at concentrations much lower in LS-174 cells (2.5-5.0 micro mol/L) than in WiDr cells (50-100 micro mol/L). In all cell lines studied, alpha-tocopherol and N-acetylcysteine inhibited the effects of beta-carotene on NF-kappaB, cell growth and apoptosis, and normalized the increased expression of c-myc induced by the carotenoid. These data suggest that the redox regulation of NF-kappaB induced by beta-carotene is involved in the growth-inhibitory and proapoptotic effects of the carotenoid in tumor cells.

Topics: Acetylcysteine; Adenocarcinoma; Apoptosis; beta Carotene; Colonic Neoplasms; Genes, myc; HL-60 Cells; Humans; NF-kappa B; Oxidation-Reduction; Reactive Oxygen Species

African Americans have the highest incidence of colon cancer among United States racial/ethnic groups, but these disparities are largely unexplained. This report describes associations of micronutrients with colon cancer risk in African Americans and whites using data from a case-control study in North Carolina. Incident cases of histologically confirmed colon cancer, age 40-80 years (n = 613), and matched controls (n = 996) were interviewed in person to elicit information on potential colon cancer risk factors. A previously validated food frequency questionnaire adapted to include regional foods was used to assess diet over the year prior to diagnosis or interview date. Micronutrient exposure included food sources and dietary supplements. Multivariate logistic regression models estimated energy-adjusted and non-energy-adjusted odds ratios (ORs). African Americans reported lower mean micronutrient intakes than whites, primarily due to larger contributions from dietary supplements in whites. Controls generally reported higher micronutrient intakes than cases; however, these differences were only statistically significant for whites. In whites, high beta-carotene, vitamin C, and calcium intakes were associated with 40-60% reductions in colon cancer risk when contrasting highest to lowest quartiles in both energy-adjusted and non-energy-adjusted models, e.g., OR = 0.4 (95% confidence interval, 0.3-0.6) for the highest quartile of calcium in the energy-adjusted model. In African Americans, vitamins C and E were strongly inversely associated using both statistical approaches: high vitamin E intake was associated with a 70% reduced risk for colon cancer, and the OR comparing the highest to lowest quartiles of vitamin C was 0.5 (95% confidence interval, 0.3-0.8). Folate and lutein were not statistically significantly associated with colon cancer risk in either racial group. These results suggest that at high intakes, micronutrients commonly found in plant and other foods (in particular, beta-carotene, vitamin C, and calcium in whites and vitamins C and E in African Americans) exhibit independent associations consistent with 30-70% reductions in colon cancer risk.

Topics: Adult; Aged; Ascorbic Acid; beta Carotene; Black or African American; Calcium, Dietary; Colonic Neoplasms; Dietary Supplements; Feeding Behavior; Female; Humans; Logistic Models; Male; Micronutrients; Middle Aged; North Carolina; Risk Factors; Vitamin E; White People

In this study, we examined possible mechanisms of caspase activation during carotenoid-induced apoptosis in tumor cells. We found that beta-Carotene induces apoptosis by the activation of caspase-3 in human leukemia (HL-60), colon adenocarcinoma (HT-29) as well as melanoma (SK-MEL-2) cell lines. This activation is dose dependent and follows that of caspase-8 and caspase-9. Although caspase-8 cleavage is an early event, reaching its maximum activation at 3 h, caspase-9 reaches its maximum activation only at 6 h. The addition of IETD-CHO, a caspase-8-specific inhibitor, completely prevents beta-Carotene-induced apoptosis, whereas only a partial prevention was observed in the presence of LEHD-CHO, a caspase-9-specific inhibitor. beta-Carotene activates caspase-9 via cytochrome c release from mitochondria and loss of mitochondrial membrane potential (Dym). Concomitantly, a dose-dependent decrease in the antiapoptotic protein Bcl-2 and a dose-dependent increase in the cleaved form of BID (t-BID) are observed. Moreover, NF-kB activation is involved in beta-Carotene-induced caspase cascade. These results support a pharmacological role for beta-Carotene as a candidate antitumor agent and show a possible sequence of molecular events by which this molecule may induce apoptosis in tumor cells.

Topics: Adenocarcinoma; Apoptosis; beta Carotene; BH3 Interacting Domain Death Agonist Protein; Carrier Proteins; Caspase 3; Caspase 8; Caspase 9; Caspases; Colonic Neoplasms; Cytochromes c; Enzyme Activation; Enzyme Inhibitors; HL-60 Cells; Humans; Melanoma; Membrane Potentials; Mitochondria; Neoplasms; NF-kappa B; Proto-Oncogene Proteins c-bcl-2; Tumor Cells, Cultured

The structures of two novel 3,4-seco-lanostane-type triterpenes isolated from the sclerotium of Poria cocos were established to be 16alpha-hydroxy-3,4-seco-lanosta-4(28),8,24-triene-3,21-dioic acid (1; poricoic acid G) and 16alpha-hydroxy-3,4-seco-24-methyllanosta-4(28),8,24(24(1))-triene-3,21-dioic acid (2; poricoic acid H) on the basis of spectroscopic methods. These two, and eight other known compounds isolated from the sclerotium, poricoic acid B (3), poricoic acid A (4), tumulosic acid (5), dehydrotumulosic acid (6), 3-epidehydrotumulosic acid (7), polyporenic acid C (8), 25-hydroxy-3-epidehydrotumulosic acid (9), and dehydroabietic acid methyl ester (10), showed potent inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). Evaluation of the cytotoxicity of compounds 1 and 4 against human cancer cell lines revealed that 1 was significantly cytotoxic to leukemia HL-60 cells [GI(50) (concentration that yields 50% growth) value 39.3 nM], although it showed only moderate cytotoxicity to the other cells. Compound 4 exhibited moderate cytotoxicity to all of the cancer cell lines tested.

Topics: Antineoplastic Agents, Phytogenic; Brain Neoplasms; Chromatography, High Pressure Liquid; Colonic Neoplasms; Drug Screening Assays, Antitumor; Female; Humans; Japan; Kidney Neoplasms; Lanosterol; Leukemia, Myeloid; Lung Neoplasms; Melanoma; Molecular Conformation; Molecular Structure; Nuclear Magnetic Resonance, Biomolecular; Ovarian Neoplasms; Plants, Medicinal; Polyporaceae; Spectrophotometry, Infrared; Spectrophotometry, Ultraviolet; Triterpenes; Tumor Cells, Cultured

UV radiation from sunlight is the most potent environmental risk factor in skin cancer pathogenesis. In the present study the ability of an algal extract to protect against UVA-induced DNA alterations was examined in human skin fibroblasts (1BR-3), human melanocytes (HEMAc) and human intestinal CaCo-2 cells. The protective effects of the proprietary algal extract, which contained a high level of the carotenoid astaxanthin, were compared with synthetic astaxanthin. DNA damage was assessed using the single cell gel electrophoresis or comet assay. In 1BR-3 cells, synthetic astaxanthin prevented UVA-induced DNA damage at all concentrations (10 nM, 100 nM, 10 microM) tested. In addition, the synthetic carotenoid also prevented DNA damage in both the HEMAc and CaCo-2 cells. The algal extract displayed protection against UVA-induced DNA damage when the equivalent of 10 microM astaxanthin was added to all three-cell types, however, at the lower concentrations (10 and 100 nM) no significant protection was evident. There was a 4.6-fold increase in astaxanthin content of CaCo-2 cells exposed to the synthetic compound and a 2.5-fold increase in cells exposed to algal extract. In 1BR-3 cells, exposure to UVA for 2 h resulted in a significant induction of cellular superoxide dismutase (SOD) activity, coupled with a marked decrease in cellular glutathione (GSH) content. However pre-incubation (18 h) with 10 microM of the either the synthetic astaxanthin or the algal extract prevented UVA-induced alterations in SOD activity and GSH content. Similarly, in CaCo-2 cells a significant depletion of GSH was observed following UVA-irradiation which was prevented by simultaneously incubating with 10 microM of either synthetic astaxanthin or the algal extract. SOD activity was unchanged following UVA exposure in the intestinal cell line. This work suggests a role for the algal extract as a potentially beneficial antioxidant.

Topics: Antioxidants; beta Carotene; Colonic Neoplasms; Comet Assay; DNA Damage; Eukaryota; Glutathione; Humans; Intestinal Mucosa; Plant Extracts; Superoxide Dismutase; Tumor Cells, Cultured; Ultraviolet Rays; Xanthophylls

Although the pharmacological role of beta-carotene in the prevention and treatment of colon cancer has received increasing attention, little is known about the molecular mechanisms of action of this carotenoid. The present study demonstrates that beta-carotene, a natural pigment widely present in fruit and vegetables, inhibits the growth of several human colon adenocarcinoma cell lines (COLO 320 HSR, LS-174, HT-29 and WiDr) by inducing cell cycle arrest in G(2)/M phase and apoptosis. These effects were dose and time dependent and strictly related to cell ability to accumulate the carotenoid. COLO 320 HSR cells incorporated beta-carotene to a greater extent than LS-174, HT-29 and WiDr cells and, concomitantly, they exhibited a higher sensitivity to the growth inhibitory effects of the carotenoid. At inhibitory concentrations beta-carotene reduced the expression of cyclin A, a key regulator of G(2)/M progression. Neither p21 nor p27, two cyclin kinase inhibitors, were significantly modified by carotenoid treatment. With respect to apoptosis induction, decreased levels of the apoptosis blocking proteins Bcl-2 and Bcl-xL were also observed. On the other hand, no changes in expression of the apoptosis promoter protein Bax were detected. This study represents a novel aspect of the biological profile of beta-carotene and a new step in elucidating the underlying molecular mechanisms of its antitumor action. In addition, since cell growth inhibitory effects were reached at beta-carotene concentrations achievable in vivo following its supplementation, this study provides a rational approach for the use of beta-carotene in colon cancer.

Topics: Adenocarcinoma; Apoptosis; beta Carotene; Cell Cycle; Cell Cycle Proteins; Cell Division; Colonic Neoplasms; Cyclin A; Down-Regulation; Flow Cytometry; Humans; Immunohistochemistry; Proto-Oncogene Proteins c-bcl-2; Tumor Cells, Cultured

To understand differential tissue distribution of retinoids and carotenoids, as it might influence biological processes in humans, we developed and demonstrated a method for measuring them in selected human tissues. The method includes internal standards and a secondary reference standard to eliminate the need for external standard calibration and to minimize sample-handling errors. Tissues were digested (saponified) in ethanolic KOH. Retinol and beta-carotene were extracted with organic solvent containing internal standards. Analytes were separated using isocratic liquid chromatography and quantified at 325 nm for retinol and 450 nm for beta-carotene. Plasma was analyzed in a similar way but without saponification. Retinal-O-ethyloxime and beta-apo-12'-carotenal-O-t-butyloxime served as internal standards. Plasma, breast, and fat from breast surgery patients and colon, liver, muscle, and fat from colon surgery patients were analyzed. Within-day relative standard deviations (RSDs) for plasma were <0.04 for beta-carotene and <0.03 for retinol, between-day RSDs were <0.05 for beta-carotene and <0.04 for retinol. Saponification ensured complete extraction of retinol and beta-carotene and removal of triglycerides that "foul" chromatographic columns. It seems retinol and beta-carotene concentrations in tissues and blood of cancer patients are the same or higher than those in corresponding tissues of patients without these cancers.

Topics: Adult; Aged; beta Carotene; Blood Chemical Analysis; Breast Neoplasms; Chromatography, High Pressure Liquid; Colonic Neoplasms; Female; Humans; Male; Middle Aged; Reference Standards; Spectrophotometry; Tissue Distribution; Vitamin A

This is the first report demonstrating a relationship between apoptosis induction and changes of intracellular redox potential in the growth-inhibitory effects of high concentrations of beta-carotene in a tumor cell line. beta-Carotene inhibited the growth of human WiDr colon adenocarcinoma cells in a dose- and time-dependent manner, induced apoptosis, and blocked Bcl-2 expression. These effects were accompanied by an enhanced production of intracellular reactive oxygen species (ROS). The addition of the antioxidant alpha-tocopherol blocked both the pro-oxidant and the growth-inhibitory effects of the carotenoid. These findings suggest that beta-carotene may act as an inductor of apoptosis by its pro-oxidant properties.

Topics: Adenocarcinoma; Antioxidants; Apoptosis; bcl-2-Associated X Protein; bcl-X Protein; beta Carotene; Cell Division; Cell Survival; Colonic Neoplasms; Dose-Response Relationship, Drug; Free Radicals; Growth Inhibitors; Humans; Oxidants; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-bcl-2; Reactive Oxygen Species; Tumor Cells, Cultured; Vitamin E

Epidemiological studies suggest that beta-carotene is able to modulate the risk of cancer. A number of in vitro studies reported that beta-carotene inhibits the growth of cancer cells; however, so far little is known about the molecular mechanisms of the antiproliferative effect of beta-carotene. Here we have investigated the effects of two beta-carotene preparations, (i) beta-carotene dissolved in tetrahydrofuran (final concentration in cell culture medium: 0.5%) and (ii) beta-carotene incorporated in a water dispersible bead form, on cultured human colon carcinoma cells HT29. The treatment of cells with beta-carotene up to 30 microM for 72 h led to a significant increase in the cellular beta-carotene concentration and formation of retinol. Beta-Carotene showed only low cytotoxicity for confluent cells tested up to 30 microM, but at dietary relevant concentrations for the intestinal tract (10, 30 microM) beta-carotene was strongly cytotoxic for growing cells and induced apoptosis in HT29 cells as assessed by the Annexin-V assay (the maximal effect was observed 15 h after treatment with beta-carotene). Exposure of cells to retinol at concentrations yielding cellular retinol levels similar to those observed by beta-carotene treatment had no antiproliferative or cytotoxic effect. Furthermore, beta-carotene did not affect the activation of the extracellular signal-regulated kinases (ERK1 and ERK2) that are essential for cellular growth. In summary, beta-carotene can inhibit growth of human colon carcinoma cells in vitro by induction of apoptosis in proliferating cells.

Topics: Apoptosis; beta Carotene; Cell Division; Colonic Neoplasms; Flow Cytometry; Formazans; Growth Inhibitors; HT29 Cells; Humans; Mitogen-Activated Protein Kinases; Phosphorylation; Tetrazolium Salts; Vitamin A

Carotenoids have numerous biological properties that may underpin a role for them as chemopreventive agents. However, except for beta-carotene, little is known about how dietary carotenoids are associated with common cancers, including colon cancer.. The objective of this study was to evaluate associations between dietary alpha-carotene, beta-carotene, lycopene, lutein, zeaxanthin, and beta-cryptoxanthin and the risk of colon cancer.. Data were collected from 1993 case subjects with first primary incident adenocarcinoma of the colon and from 2410 population-based control subjects. Dietary data were collected from a detailed diet-history questionnaire and nutrient values for dietary carotenoids were obtained from the US Department of Agriculture-Nutrition Coordinating Center carotenoid database (1998 updated version).. Lutein was inversely associated with colon cancer in both men and women [odds ratio (OR) for upper quintile of intake relative to lowest quintile of intake: 0.83; 95% CI: 0.66, 1.04; P = 0.04 for linear trend]. The greatest inverse association was observed among subjects in whom colon cancer was diagnosed when they were young (OR: 0.66; 95% CI: 0.48, 0.92; P = 0.02 for linear trend) and among those with tumors located in the proximal segment of the colon (OR: 0.65; 95% CI: 0.51, 0.91; P < 0.01 for linear trend). The associations with other carotenoids were unremarkable.. The major dietary sources of lutein in subjects with colon cancer and in control subjects were spinach, broccoli, lettuce, tomatoes, oranges and orange juice, carrots, celery, and greens. These data suggest that incorporating these foods into the diet may help reduce the risk of developing colon cancer.

Topics: Adenocarcinoma; Age Factors; Aged; Anticarcinogenic Agents; beta Carotene; Carotenoids; Colonic Neoplasms; Cryptoxanthins; Diet; Diet Surveys; Humans; Lutein; Lycopene; Middle Aged; Phytotherapy; Risk Factors; Smoking; Utah; Vegetables; Xanthophylls; Zeaxanthins

We have reported protective effects of dietary administration of a powder "CHRP" containing high amounts of beta-cryptoxanthin and hesperidin prepared from a Satsuma mandarin (Citrus unshiu Marc.) juice on azoxymethane (AOM)-induced rat aberrant crypt foci through suppression of crypt cell proliferation and/or induction of detoxifying enzymes. In the present study, we investigated the modifying effects of a commercial Satsuma mandarin (Citrus unshiu Marc.) juice (MJ) and those of MJ2 and MJ5, which were prepared from MJ and are richer in beta-cryptoxanthin and hesperidin than MJ, on the occurrence of colonic tumors induced by AOM in male F344 rats. Rats were given 2 weekly s.c. injections of AOM (20 mg/kg body weight) to induce colonic neoplasms. They also received MJ, MJ2, or MJ5 as a drinking water at night for 36 weeks, starting 1 week after the last dosing of AOM. AOM exposure produced colonic adenocarcinoma with an incidence of 69% and a multiplicity of 0.76 +/- 0.57/rat at week 38. MJ, MJ2, and MJ5 administration significantly reduced the frequency of colonic carcinoma [MJ: 35% (49% reduction), p < 0.02; MJ2: 20% (64% reduction), p = 0.0028; and MJ5: 15% (78% reduction), p < 0.00021] and multiplicity [MJ: 0.40 +/- 0.58 (47% reduction), p < 0.05; MJ2: 0.25 +/- 0.43 (67% reduction), p < 0.005; and MJ5: 0.15 +/- 0.36 (80% reduction), p < 0.001]. Also, the numbers of cancer cells positive for proliferative cell nuclear antigen (PCNA) and cyclin D1 in colonic tumors were lowered by these treatments. In addition, treatment with MJ, MJ2, or MJ5 significantly increased apoptotic index in colonic adenocarcinoma. These findings might suggest effective chemopreventive ability of MJs, especially MJ5, in colon tumorigenesis.

Topics: Adenocarcinoma; Adenoma; Animals; Anticarcinogenic Agents; Apoptosis; Azoxymethane; beta Carotene; Beverages; Carcinogens; Citrus; Colonic Neoplasms; Cryptoxanthins; Cyclin D1; Hesperidin; Male; Proliferating Cell Nuclear Antigen; Rats; Rats, Inbred F344; Xanthophylls

Various natural carotenoids were proven to have anticarcinogenic activity. Epidemiological investigations have shown that cancer risk is inversely related to the consumption of green and yellow vegetables and fruits. Since beta-carotene is present in abundance in these vegetables and fruits, it has been investigated extensively as possible cancer preventive agent. However, various carotenoids which co-exist with beta-carotene in vegetables and fruits also have anti-carcinogenic activity. And some of them, such as alpha-carotene, showed higher potency than beta-carotene to suppress experimental carcinogenesis. Thus, we have carried out more extensive studies on cancer preventive activities of natural carotenoids in foods; i.e., lutein, lycopene, zeaxanthin and beta-cryptoxanthin. Analysis of the action mechanism of these natural carotenoids is now in progress, and some interesting results have already obtained; for example, beta-cryptoxanthin was suggested to stimulate the expression of RB gene, an anti-oncogene, and p73 gene, which is known as one of the p53-related genes. Based on these results, multi-carotenoids (mixture of natural carotenoids) seems to be of interest to evaluate its usefulness for practice in human cancer prevention.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Anticarcinogenic Agents; beta Carotene; Carotenoids; Colonic Neoplasms; Cryptoxanthins; Disease Models, Animal; Fruit; Humans; Lutein; Lycopene; Methylnitrosourea; Mice; Rats; Rats, Inbred F344; Skin Neoplasms; Tetradecanoylphorbol Acetate; Vegetables; Xanthophylls; Zeaxanthins

The effects of combinations between eicosapentaenoic acid (EPA) and beta-carotene on cell growth and lipid peroxidation were investigated in human WiDr colon adenocarcinoma cells. EPA alone was able to inhibit the growth of WiDr cells in a dose- and time-dependent manner. Such an inhibition involved fatty acid peroxidation, as shown by the remarkable increase in the levels of Malondialdehyde (MDA) in EPA-treated cells. Beta-carotene was capable of reducing the growth inhibitory effects of EPA and the levels of MDA in a dose- and a time-dependent manner. In addition, EPA increased beta-carotene consumption in WiDr cells. This study provides evidence that beta-carotene can antagonize the effects of EPA on colon cancer cell growth and lipid peroxidation.

Topics: Adenocarcinoma; beta Carotene; Cell Division; Colonic Neoplasms; Eicosapentaenoic Acid; Humans; Kinetics; Lipid Peroxidation; Malondialdehyde; Time Factors; Tumor Cells, Cultured

Dietary determinants of colorectal mucosa proliferation were studied in 69 subjects previously operated for at least two sporadic colon adenomas. Information on recent dietary habits was collected by a validated food frequency questionnaire, and proliferation was measured by [3H]thymidine incorporation in colorectal biopsies by determining the labeling index (LI) and the percentage of LI in the upper part of the crypt, two parameters that are increased in subjects at high risk of colon cancer. The LI was significantly higher in women as compared with men (P = 0.01). Diet showed several associations with colorectal mucosa proliferation: (a) subjects in the highest tertile of fish consumption had a significantly lower LI (P = 0.0013) compared with those in the lower tertiles [5.20 +/- 1.87 versus 6.80 +/- 2.18 (mean +/- SD)]; (b) subjects with a low red meat consumption had lower proliferation in the upper part of the crypt [2.38 +/- 2.10, 5.30 +/- 4.62, and 5.89 +/- 4.82 in the low, middle, and high tertile of consumption, respectively (mean +/- SD); P = 0.0093]; (c) according to estimated nutrient intakes, the LI was lower in subjects reporting a high intake of starch (P = 0.006) and higher in subjects with a low intake of beta-carotene (P = 0.002). The results show that subjects reporting a diet rich in fish, starch, and beta-carotene and low in red meat had lower colorectal mucosa proliferation and a normal pattern of proliferation along the crypt. Given the correlation between colorectal proliferative activity and colon cancer risk, such a dietary pattern might be beneficial for subjects at high risk of colon cancer.

Topics: Adenomatous Polyps; Adult; Aged; Animals; Antioxidants; beta Carotene; Biopsy; Cell Division; Colon; Colonic Neoplasms; Colonic Polyps; Dietary Carbohydrates; Feeding Behavior; Female; Fishes; Food; Humans; Intestinal Mucosa; Male; Meat; Middle Aged; Rectum; Risk Factors; Sex Factors; Starch; Surveys and Questionnaires; Thymidine; Tritium

Beta-cryptoxanthin (betaCx), one of 4 major carotenoids in the blood, was investigated for anticarcinogenic activity in F344 rats. Four groups of 25 rats each received an intrarectal dose of 2 mg of N-methylnitrosourea 3 times a week for 5 weeks, and were fed the diet supplemented with 0 ppm (control), 25 ppm, 5 ppm or 1 ppm betaCx throughout the experiment. The colon cancer incidence at week 30 was significantly lower in the betaCx (25 ppm) diet group, but not in the betaCx (5 ppm) and betaCx (1 ppm) diet groups, than in the control diet group: 68%, 84%, 80% vs. 96%. The results suggested that dietary betaCx may affect colon carcinogenesis after accumulation in the colonic mucosa, perhaps due to absorption from the colon as well as the small intestine.

Topics: Animals; Anticarcinogenic Agents; beta Carotene; Colonic Neoplasms; Cryptoxanthins; Female; Methylnitrosourea; Rats; Rats, Inbred F344; Xanthophylls

(1) To compare tissue and plasma carotenoids status of healthy subjects and subjects with pre-cancer and cancer lesions; (2) to evaluate the effect of beta-carotene supplementation on the concentrations of other carotenoids in tissue (luteine + zeaxanthin, cryptoxanthin, lycopene, alpha-carotene) and in plasma and also retinol and alpha-tocopherol levels.. Eighteen subjects were divided into three groups on the basis of colonoscopy and histological analytical findings: four healthy subjects (control group A); seven subjects affected by adenomatous polyps (group B with pre-cancer lesions); seven subjects suffering from colonic cancer (group C). Blood and colonic biopsy samples were taken (of colon and rectal mucosa) before and after beta-carotene supplementation in all subjects. Groups A and B received a daily dose of beta-carotene (30 mg/die) for 43 d. Group C's supplementation was terminated at the time which was performed, usually within 15 d. The tissue and plasma concentration of carotenoids, retinol and alpha-tocopherol were determined by high-performance liquid chromatography.. The tissue concentrations of each carotenoid were similar in all the intestinal sites examined as regards groups A and B, although there was a high degree of intra individual variability within each group. Only beta-carotene made significant increases (P < 0.001) after supplementation. The subjects with cancer show tissue levels for each carotenoid lower than those of healthy subjects or subjects with polypous. The plasma levels of alpha-tocopherol did not change after supplementation while significant increases were noted of retinol, alpha-carotene (P < 0.01) and of beta-carotene (P < 0.001).. The patients with colonic cancer seemed to undergo a significant reduction in their antioxidant reserves with respect to the normal subjects and or polyps. We can confirm that oral B-carotene supplementation induces also an increase in plasma alpha-carotene in all groups.

Topics: Adenomatous Polyposis Coli; Adult; Aged; beta Carotene; Carotenoids; Colonic Neoplasms; Female; Humans; Intestinal Mucosa; Male; Middle Aged; Precancerous Conditions; Vitamin A; Vitamin E

Comparative international epidemiological data indicate that the difference between the highest and lowest colon cancer incidence is approximately 10-fold. This suggests that the dominant causes of colon cancer are environmental rather than genetic in origin, with the dominant environmental cause being the typical diet of Western industrialized countries. Many epidemiological and experimental studies have suggested an important role for dietary fiber in the prevention of colon cancer. Using the Fischer-344 rat as the experimental model, data clearly demonstrate a strong protective effect of a diet that is low in fat, high in fiber and high in calcium (low-risk diet). Such a diet prevents the development of both preneoplastic aberrant crypt foci (ACF) and colon tumors. Recent experiments have also demonstrated a direct relationship between a ras point mutation in ACF at different stages of rat colon carcinogenesis, and a ras point mutation that is subsequently present in colon tumors. Using wheat bran as the model dietary fiber source, its effects were compared to the effects of psyllium, phytic acid, vitamin E, beta-carotene, folic acid, alone or in combination, for their ability to prevent colon cancer in rats on high-risk Western-style diets. Our studies clearly demonstrated the ability of wheat bran to reduce ACF and colon tumors in rats that consumed high-fat, Western-style diets. Although phytic acid, which is a constituent of wheat bran, alone demonstrated strong cancer-preventive potential, our experiments provided evidence for the cancer-preventive effect of the crude fiber fraction that is independent of the effect of phytic acid. The synergistic combination of wheat bran with the soluble fiber psyllium led to enhanced protection; while the combination of wheat bran with beta-carotene showed only an additive effect. Beta-carotene appeared to show higher protection than wheat bran at an intake level that is nutritionally relevant to humans, suggesting the possibility of using beta-carotene to enhance the effects of dietary fiber in high-risk Western populations. Using ACF as an intermediate endpoint, it was also shown that vitamin E and beta-carotene appear to inhibit progression of ACF to colon cancer, while wheat bran and folic acid appeared to have weak cancer-preventive potential at this late stage of carcinogenesis. In conclusion, wheat bran alone, or in combination with psyllium, appears to have greater potential to inhibit earlier phases of

Topics: Animals; Azoxymethane; beta Carotene; Carcinogens; Carotenoids; Colon; Colonic Neoplasms; Diet; Dietary Fats; Dietary Fiber; Genes, ras; Humans; Intestinal Mucosa; Phytic Acid; Precancerous Conditions; Psyllium; Rats; Rats, Inbred F344; Risk Factors

Experiments were conducted to determine the effect of beta-carotene on human colon cancer cells in vitro. beta-Carotene solubilized in tetrahydrofuran (THF) was determined to be cytotoxic for three different cell lines: LS 180, SW 620, and HCT-15. The number of LS 180 and SW 620 cells surviving treatment with 2.9 microM beta-carotene was significantly reduced relative to THF-treated cells, and a similar reduction was achieved in HCT-15 cells with use of 5.8 microM beta-carotene. These concentrations are in the range achieved in serum of individuals supplemented with beta-carotene at 30 mg/day. There was no beta-carotene cytotoxicity in the concentration range that characterizes serum of unsupplemented individuals. Vitamin E at > 200 microM was not cytotoxic and at higher concentrations slightly stimulated proliferation of all three cell lines. Exposure of cells to vitamin E did not diminish the cytotoxicity of beta-carotene, suggesting that the toxic effect of beta-carotene is not due to prooxidant activity. Percent cytotoxicity was increased by extending the duration of exposure of cells to beta-carotene. Interestingly, beta-carotene cytotoxicity decreased with increasing cell density. This density-dependent toxicity was attributable to a higher beta-carotene concentration per cell for cells plated at lower densities. Thus toxicity of beta-carotene for colon cancer cells is dose, time, and cell density dependent and occurs in vitro at concentrations that can be achieved safely in humans.

Topics: beta Carotene; Cell Division; Cell Survival; Chromatography, High Pressure Liquid; Colonic Neoplasms; Furans; Humans; Solubility; Tumor Cells, Cultured; Vitamin E

The modulating effect of the combined dietary feeding of beta-carotene and perilla oil, which is rich in alpha-linolenic acid, on the development of azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) was investigated in male F344 rats. Rats received oral administration of beta-carotene (0, 50 or 200 mg/kg body weight/day) and fed a basal diet containing either 12% olive oil, 3% perilla oil plus 9% olive oil, or 12% perilla oil. A dose-dependent suppressive effect of perilla oil was found. The numbers of ACF were 42.0 and 18.4% of those of the 12% olive oil-fed controls in the rats fed 3% perilla oil plus 9% olive oil and 12% perilla oil, respectively. The development of ACF was also reduced significantly by the addition of dietary beta-carotene in each of the oil-fed groups (P < 0.05, respectively). The suppression by the combination of beta-carotene and perilla oil was synergistic, as the numbers of ACF were 12.9 and 8.9% of those of the 12% olive oil-fed controls in beta-carotene-treated rats fed 3% perilla oil plus 9% olive oil and 12% perilla oil, respectively. beta-carotene plus perilla oil also suppressed the numbers of silver-stained nucleolar organizer regions and the expression of ras mRNA in the colonic mucosa (cell proliferation biomarkers). Following administration of beta-carotene, a significant increase in the concentration of intact beta-carotene molecules was found in the colonic mucosa, livers, and sera. However, no accumulation of retinoids was observed in the colonic mucosa, suggesting that the inhibitory effect may not be related to the provitamin A activity. These results suggest that the combination of beta-carotene and perilla oil may be useful in the prevention of colon cancer.

Topics: Administration, Oral; alpha-Linolenic Acid; Animals; Anticarcinogenic Agents; Azoxymethane; beta Carotene; Biomarkers; Carcinogens; Colon; Colonic Neoplasms; Drug Synergism; Genes, ras; Intestinal Mucosa; Liver; Male; Nucleolus Organizer Region; Olive Oil; Plant Oils; Rats; Rats, Inbred F344; Retinoids; Vitamin A

In a previous study we reported that beta-carotene solubilized in tetrahydrofuran (THF) is toxic for human colonic tumor cells in vitro using media containing 10% fetal calf serum (FCS). Cytotoxicity was evident using beta-carotene concentrations that are achieved in human serum as a result of supplementation with 30 mg beta-carotene/day. In an attempt to determine the mechanism for this toxicity we investigated the effect of beta-carotene when present in human serum as a result of dietary supplementation. This effect was compared to that observed for cells incubated in THF-solubilized beta-carotene. The results indicate that human serum from subjects with a high concentration of beta-carotene is not cytotoxic. Subsequent analysis revealed that in contrast to the results using FCS, THF-solubilized beta-carotene is not cytotoxic in the presence of human serum. In addition, the effect observed with FCS is blunted with increasing FCS concentration from > or = 90% cytotoxicity using 10% FCS to 36% using 100% FCS. The difference in results obtained using FCS and human serum may be due to a serum component that is relatively lacking in FCS as compared to human serum.

Topics: Antineoplastic Agents; beta Carotene; Cell Survival; Colonic Neoplasms; Culture Media; Food, Fortified; Furans; Humans; Time Factors; Tumor Cells, Cultured

We determined whether intakes of the main dietary carotenoids (alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein plus zeaxanthin, and lycopene) and of vitamins A, C, and E were associated with the prevalence of colorectal adenomas among male and female members of a prepaid health plan in Los Angeles who underwent sigmoidoscopy (n = 488 matched pairs). Participants, ages 50-74 years, completed a 126-item semiquantitative food-frequency questionnaire and a non-dietary questionnaire from 1991 to 1993. In the univariate-matched analysis, alpha-carotene, beta-carotene (with and without supplements), beta-cryptoxanthin, lutein plus zeaxanthin, vitamin A (with and without supplements), and vitamin C (with and without supplements) were associated with a decreased prevalence of colorectal adenomas. After adjustment for intake of calories, saturated fat, folate, fiber, and alcohol, and for current smoking status, body mass index, race, physical activity, and use of nonsteroidal anti-inflammatory drugs, only beta-carotene including supplements was inversely associated with adenomas (odds ratio (OR), 0.6; 95% confidence interval (CI), 0.41.1; trend, P= 0.04; ORs compare highest to lowest quartiles0; vitamin C showed a weaker inverse association (OR, 0.8; 95% CI, 0.5-1.5; trend, P = 0.08); and the remaining compounds were no longer clearly associated with risk. After including beta-carotene with supplements and vitamin C simultaneously in the mutivariate model, the association of beta-carotene with supplements with adenomas was weakened (OR, 0.8; 95% CI, 0.5-1.3; trend P = 0.15), and vitamin C was no longer associated with risk. These data provide only modest support for a protective association of beta-carotene with colorectal adenomatous polyps.

Topics: Adenoma; Aged; Anticarcinogenic Agents; Ascorbic Acid; beta Carotene; Carotenoids; Case-Control Studies; Colonic Neoplasms; Cryptoxanthins; Diet; Feeding Behavior; Female; Humans; Los Angeles; Lutein; Lycopene; Male; Middle Aged; Multivariate Analysis; Prevalence; Rectal Neoplasms; Risk Factors; Sigmoidoscopy; Vitamin A; Vitamin E; Xanthophylls; Zeaxanthins

Inhibitory effect of four carotenoids prevalent in human blood and tissues against the formation of colonic aberrant crypt foci was examined in Sprague-Dawley rats. They received three intrarectal doses of N-methylnitrosourea in weak 1, and a daily gavage of de-escalated doses of carotenoids during weeks 2 and 5. Lycopene, lutein, alpha-carotene and palm carotenes (a mixture of alpha-carotene, beta-carotene and lycopene) inhibited the development of aberrant crypt foci quantitated at week 6, but beta-carotene did not. The results suggested that lycopene and lutein in small doses may potentially prevent colon carcinogenesis.

Topics: Animals; Anticarcinogenic Agents; beta Carotene; Carotenoids; Colonic Neoplasms; Female; Intestinal Mucosa; Lutein; Lycopene; Neoplasms, Experimental; Precancerous Conditions; Rats; Rats, Sprague-Dawley

The quantity of beta-carotene (BC) accumulated in colonic polyps and colonic cancerous tissue in humans in situ was determined relative to the quantity accumulated in normal colon and rectal tissue. Serum concentration of BC, retinol, and alpha-tocopherol and tissue BC concentration were determined by high-performance liquid chromatography in samples obtained before and after oral supplementation with BC (30 mg/day). The serum BC and retinol concentrations significantly increased in response to supplementation in control, polyp, and cancer patients, but there was no change in serum alpha-tocopherol concentration. The BC concentration in tissue (colon, rectum, and tumor) of cancer patients was significantly less than that in tissue samples from control and polyp patients. Relative to baseline values, BC accumulated to a significant extent in tissues from all patients, including polyp and tumor tissue, during supplementation. The results indicate that BC does accumulate in colonic neoplastic tissue in humans and may potentially be utilized to augment cytotoxicity of chemotherapeutics or to prevent malignant transformation of cells.

Topics: Adenomatous Polyps; Aged; Aged, 80 and over; beta Carotene; Carotenoids; Chromatography, High Pressure Liquid; Colon; Colonic Neoplasms; Colonic Polyps; Female; Humans; Intestinal Mucosa; Male; Middle Aged; Rectum; Vitamin A; Vitamin E

Selenium deficiency has been associated with cancer risk in several organs. This association was investigated in neoplasia of the colorectum.. A case-control study is reported with two patient series, colorectal cancer and colorectal adenomatous polyps, and a control group found to be free of colorectal neoplasia. Diagnosis was determined by colonoscopy and histologic review of suspected neoplasms. Serum drawn at the time of colonoscopy was subsequently assayed for selenium content, and quartiles based on selenium were defined. Crude and adjusted odds ratios with 95 percent confidence intervals for adenoma related to selenium were calculated, controlling for known or suspected risk factors including gender, age, race, body mass index, family history, tobacco use, alcohol consumption, serum beta carotene, serum alpha tocopherol, and serum ferritin.. There were 138 controls who had no neoplastic disease, 139 adenoma patients, and 25 cancer patients. For adenoma, comparing higher quartiles of selenium to the first (lowest selenium), the adjusted odds ratio for the second quartile was 1.7 (95 percent confidence interval, 0.8-3.7), the third quartile was 1.4 (0.7-3.2), and the fourth (highest selenium) quartile was 1.8 (0.9-4). The odds ratios for cancer patients were 0.8 for the second quartile, 1 for the third quartile, and 1.7 for the fourth quartile.. No trend could be detected toward a protective effect of higher levels of serum selenium for colonic benign or malignant tumors.

Topics: Adenoma; Adenomatous Polyps; Adult; Age Factors; Aged; Aged, 80 and over; Alcohol Drinking; beta Carotene; Body Mass Index; Carotenoids; Case-Control Studies; Colonic Neoplasms; Colonic Polyps; Colonoscopy; Female; Ferritins; Humans; Male; Middle Aged; Odds Ratio; Racial Groups; Rectal Neoplasms; Risk Factors; Selenium; Sex Factors; Smoking; Vitamin E

Precancerous pathological changes of colon was induced by single injection in a short-term and multiple injection in a long-term intraperitoneally with 1,2-dimethylhydrazine (DMH) in NIH mice and Sprague-Dawley rats. And, protective effects of spirulina, germanium-132 and vitamin E on colon aberrant crypts induced by DMH were observed. Results showed either single injection or multiple injection with DMH could induce aberrant crypts in colon. The number of aberrant crypts scattered by short-term single injection was less than that by multiple one, and less of the aberrant crypts foci were formed by short-term single injection. Spirulina powder, germanium-132 and vitamin E all could inhibit the function of aberrant crypts of colon. In the ninth week during multiple injection with DMH, a lot of aberrant crypts of colon had been induced, and a certain amount of aberrant crypts foci had been generated. The number of aberrant crypts and aberrant crypts foci in the animals with tumor increased with the length of DMH injection. In the ninth-, 13th- and 16th-week, respectively, the number of aberrant crypts and aberrant crypts foci was significantly less in animals protected by spirulina than in positive controls (P < 0.01), but there was no significant difference between them during 21st- and 24th-week of injections.

Topics: Animals; Antineoplastic Agents, Phytogenic; beta Carotene; Carotenoids; Colonic Neoplasms; Dimethylhydrazines; Eukaryota; Male; Mice; Precancerous Conditions; Rats; Rats, Sprague-Dawley; Vitamin E

In this study we evaluated the effect of dietary administration of a high-fat, low-fiber diet (HRD) supplemented with Vitamin E, beta-carotene or folic acid and wheat bran on the growth of pre-existing aberrant crypt foci (ACF) that had been induced in Fischer-344 rats exposed to azoxymethane (AOM) and a HRD for 10 weeks. The rats (25 rats/dietary group) were fed a HRD for 2 weeks and were then given 2 subcutaneous injections of AOM (15 mg/kg body weight) while the rats continued on the HRD. After 6 weeks, rats were either maintained on the HRD (control) or crossed over to a HRD containing non-toxic levels of either Vitamin E, beta-carotene, folic acid or wheat bran. At 10, 14 and 18 weeks after the initiation of the experiment, 5 rats from each group were killed and the number of aberrant crypt foci (ACF) with different multiplicities were compared between groups. The dietary intervention was continued for 30 weeks to determine whether the inhibitory effect on the growth of ACF influenced the subsequent development of colonic tumors. The results revealed that vitamin E and beta-carotene caused a significant decrease in the number of ACF of different multiplicities when compared to the effect of the HRD alone. The decrease in the number of ACF due to folic acid and wheat bran appeared to be much smaller and in most cases was not significant. However, there was also a significant decrease in the incidence of colonic tumors and tumor multiplicity in both the vitamin E and beta-carotene groups that was not seen in the control group. The reports clearly demonstrates the ability of vitamin E and beta-carotene to inhibit the growth of colonic ACF, even in the presence of the strong promoting effect of high levels of dietary fat, using a post-initiation experimental design.

Topics: Animals; Antineoplastic Agents; beta Carotene; Carotenoids; Colonic Neoplasms; Dietary Fats; Dietary Fiber; Folic Acid; Precancerous Conditions; Rats; Rats, Inbred F344; Vitamin E

The typical high-fat, low-fiber American diet promotes colon cancer. An alternative to radical changes in dietary habits is to reinforce the diet with cancer protectors. Experiments to evaluate the effects of beta-carotene in the presence of high fat and low and high dietary levels of wheat bran fiber were designed using the Fischer-344 rat colon cancer model. Rats (20/group), were given either high fat (20% w/w), low wheat bran, fiber (1% w/w) diets, or high fat (20% w/w) high wheat bran fiber (8% w/w) diets, with different levels of beta-carotene. After 2 weeks of adaptation, half were given two weekly s.c. injections of azoxymethane (AOM, 15 mg/kg body wt); and half two weekly s.c. injections of saline. Six weeks later, five rats from each dietary group were killed to evaluate the comparative effect of different dietary regimens on the induction of colon aberrant crypt foci (ACF). The remaining rats were maintained on their respective diets for an additional 20 weeks to examine the effect on colon tumor incidence. The total number of ACF/rat in the low-fiber groups declined from 44.0 +/- 4.18 to 12.8 +/- 1.95 in response to increasing amounts of beta-carotene from 1 to 20 mg/kg diet. A similar progressive reduction in total ACF/rat was also seen in the high-fiber groups (20.8 +/- 2.92 to 9.2 +/- 0.58). ACF did not develop in the saline-exposed groups. Similarly colon tumor incidence declined from 73% to 20% in high-fiber groups and from 27% to 13% in low-fiber groups in response to increasing amounts beta-carotene from 1 to 20 mg/kg diet. The results showed that beta-carotene and wheat bran, individually and when combined, protected the colon in rats consuming high-fat, western-style diets from ACF and benign or malignant tumor formation.

Topics: Animals; Anticarcinogenic Agents; Azoxymethane; beta Carotene; Body Weight; Carotenoids; Cocarcinogenesis; Colonic Neoplasms; Dietary Fats; Dietary Fiber; Dose-Response Relationship, Drug; Male; Precancerous Conditions; Rats; Rats, Inbred F344; Triticum

High consumption of fruits and vegetables which are abundant in dietary antioxidants has been linked to a reduced incidence of colorectal cancer. A potential mechanism of dietary anticarcinogenesis involves the induction of detoxifying phase II enzymes, including NAD(P)H:quinone reductase (QR) and glutathione-S-transferase (GST). This study therefore examined the ability of the dietary antioxidant vitamins beta-carotene, alpha-tocopherol and ascorbic acid to induce cellular expression of QR and GST activities in human colon cancer cells. Colo205 cells were cultured in the presence or absence of various concentrations (10(-10) to 10(-5) M) of each antioxidative micronutrient, then assessed for cytosolic QR and GST activities and cell growth. beta-Carotene, alpha-tocopherol and ascorbic acid each resulted in dose-dependent increases in QR activity, without adverse effects upon cell proliferation. To investigate whether the ability of beta-carotene to induce QR may be attributable to its conversion to vitamin A and/or to its antioxidant capacity as a carotenoid, retinol, retinoic acid, and lycopene were similarly tested for their capacity for enzyme induction. Although retinol and retinoic acid were both noted to be antiproliferative at higher concentrations (10(-6) to 10(-5) M), both retinoids stimulated QR at physiological concentrations. Lycopene, a carotenoid which is not converted to vitamin A, was devoid of biologic activity. By contrast with the effects upon QR, GST activity was unaffected by treatment with any of the micronutrients tested in this in vitro model. The results support a hypothesis that a high dietary consumption of vitamins A, E and C may confer partial protection against colorectal cancer by the induction of specific detoxifying enzymes. The antioxidant capacity of beta-carotene appears to have less biologic impact vis-a-vis QR induction than its function as a non-toxic reservoir of vitamin A. Measurements of QR activity within the colorectal mucosa may provide an index of cancer susceptibility, and may be an appropriate surrogate endpoint biomarker for colorectal cancer prevention studies involving diet modification or specific relevant micronutrients.

Topics: Antioxidants; Ascorbic Acid; beta Carotene; Carotenoids; Colonic Neoplasms; Enzyme Induction; Glutathione Transferase; Humans; Lycopene; Micronutrients; NAD(P)H Dehydrogenase (Quinone); Tumor Cells, Cultured; Vitamin A; Vitamin E

The modulating effects of dietary feeding of two xanthophylls, astaxanthin (AX) and canthaxanthin (CX) during the postinitiation phase on colon carcinogenesis initiated with azoxymethane (AOM) were investigated in male F344 rats. Animals were initiated with AOM by weekly s.c. injections of 15 mg/kg body wt for 3 weeks and then they were fed the diets containing AX or CX at concentrations of 100 and 500 p.p.m. for 34 weeks. The others contained the groups of rats treated with AX or CX alone and untreated. At the end of the study (week 37), the incidence and multiplicity of neoplasms (adenoma and adenocarcinoma) in the large intestine of rats initiated with AOM and followed by AX or CX containing diet at a high dose (500 p.p.m.) were significantly smaller than those of rats given AOM alone (P < 0.001). In addition, AX or CX feeding significantly inhibited the development of aberrant crypt foci induced by AOM. Dietary exposure to AX or CX also decreased cell proliferation activity as revealed by measuring 5'-bromodeoxyuridine-labeling index as crypt cells, colonic mucosal ornithine decarboxylase activity and blood polyamine levels. These results indicate that AX and CX are possible chemopreventers for carcinogenesis of colon in addition to urinary bladder and oral cavity and such effects may be partly due to suppression of cell proliferation.

Topics: Animals; Azoxymethane; beta Carotene; Bromodeoxyuridine; Canthaxanthin; Carcinogens; Carotenoids; Colon; Colonic Neoplasms; Diet; Incidence; Intestinal Mucosa; Male; Ornithine Decarboxylase; Polyamines; Rats; Rats, Inbred F344; Xanthophylls

Topics: Animals; Antineoplastic Agents; beta Carotene; Carotenoids; Clinical Trials as Topic; Colonic Neoplasms; Cricetinae; Drug Approval; Humans; Mice; Rats

Data from two population-based case-control studies were used to investigate the effect of age on colon cancer risk. Dietary intake data were assessed from a study conducted in Utah (United States) between 1979 and 1983; reproductive data were assessed from a study conducted in Adelaide (Australia) between 1979 and 1980. Data from both studies were assessed for their impact on those less than 65 years of age and those 65 or more years of age. Intake of energy, fat, and protein had a greater impact on risk among older men than among younger men. Risk estimates for the upper quartile of intake relative to the lowest quartile of intake were 8.5 (95 percent confidence interval [CI] = 1.7-43.0) for energy, 8.2 (CI = 1.6-41.3) for protein, and 7.2 (CI = 1.6-31.4) for total fat for older men, while comparable risk estimates were 2.4 (CI = 0.6-9.1) for energy, 3.0 (CI = 0.7-13.6) for protein, and 1.9 (CI = 0.5-7.1) for total fat among younger men. Similar trends were seen for older women for energy and protein. beta-carotene decreased colon cancer risk among younger men (odds ratio [OR] = 0.4, CI = 0.1-1.2) and women (OR = 0.1, CI = 0.1-0.5), although not among older men (OR = 1.2, CI = 0.3-4.9) and women (OR = 1.9, CI = 0.6-64). Calcium decreased risk of colon cancer among older men (OR = 0.1, CI = < 0.1-0.8) and younger women (OR = 0.2, CI = < 0.1-0.7).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Age Factors; Aged; beta Carotene; Calcium, Dietary; Carotenoids; Case-Control Studies; Cohort Studies; Colonic Neoplasms; Confidence Intervals; Diet; Dietary Fats; Dietary Fiber; Dietary Proteins; Energy Intake; Female; Humans; Male; Maternal Age; Middle Aged; Odds Ratio; Parity; Risk Factors; South Australia; Utah

1,2-Diglycerides with long-chain fatty acid residues related to nutritional fat (LCDGs) specifically affect growth and urokinase secretion in human colonic tumor cells, but not in normal mucosa. This allows them to advance and enhance carcinogenesis in the colon and rectum. SW480 colon carcinoma cells are LCDG sensitive in the same way as primary colonic tumor cells and have therefore been used as a model system to study the mechanism of LCDG action and to search for inhibitors of tumor development in the colon. Using this model system, we have shown that the effects of LCDGs are transmitted by protein kinase C and abolished by downregulation of the enzyme. Retinol, retinoic acid, and beta-carotene in nanomolar concentrations inhibit LCDG-induced growth and urokinase secretion and block stimulation of protein kinase C. Although retinol and retinoic acid at higher concentrations also display stimulatory activity, beta-carotene does not. At 100 nM, a concentration that can easily be reached in the plasma of humans, beta-carotene reduces LCDG-induced urokinase secretion about 50%. Inasmuch as beta-carotene does not have side effects due to intrinsic activities and storage effects, beta-carotene and foods rich in carotenes could be useful in the prevention of colorectal cancer.

Topics: beta Carotene; Carotenoids; Cell Division; Colonic Neoplasms; Diglycerides; Humans; Protein Kinase C; Retinoids; Signal Transduction; Tumor Cells, Cultured; Urokinase-Type Plasminogen Activator

Colonic adenocarcinoma affects approximately 6% of adults in many Western countries. beta-Carotene (BC), a safe, inexpensive, and widely available compound, has been proposed as a cancer chemopreventive agent. To evaluate whether BC shows promise as an inhibitor of colonic carcinogenesis, we studied 20 male subjects who had previously undergone resection of colonic adenocarcinoma. Each subject received beta-carotene, 30 mg orally, daily for 6 months. Rectal mucosa was sampled at multiple intervals prior to, during, and following BC administration. Mucosal ornithine decarboxylase (ODC) activity and serum and mucosal BC concentrations were determined at each interval. ODC activity was inhibited by 44% (P < 0.05) and 57% (P < 0.01) after 2 and 9 weeks, respectively, of BC administration and remained low compared with baseline even 6 months following discontinuation of BC. Serum and mucosal BC concentrations increased as expected during BC administration and remained elevated for 6 months following BC discontinuation. The demonstrated inhibition of rectal mucosal ODC activity in these patients with resected colon cancer suggests that BC may prove useful as a cancer chemopreventive agent.

Topics: Aged; beta Carotene; Carotenoids; Colonic Neoplasms; Humans; Intestinal Mucosa; Male; Middle Aged; Ornithine Decarboxylase; Ornithine Decarboxylase Inhibitors; Prospective Studies; Rectum

The effects of physiologic concentrations of conjugated linoleic acid (CLA) and beta-carotene were assessed on human (M21-HPB, malignant melanoma; HT-29, colorectal; MCF-7, breast) cancer cells. The incubation of cancer cells with CLA showed significant reductions in proliferation (18-100%) compared to control cultures. M21-HPB and MCF-7 cell mortality was dose- and time-dependent. beta-Carotene was inhibitory to breast cells only. MCF-7 cells supplemented with CLA incorporated significantly less [3H]leucine (45%), [3H]uridine (63%) and [3H]thymidine (46%) than control cultures. M21-HPB and HT-29 cells supplemented with CLA incorporated less [3H]leucine (25-30%). These in vitro results suggest that CLA and beta-carotene may be cytotoxic to human cancer cells in vivo.

Topics: beta Carotene; Breast Neoplasms; Carotenoids; Cell Division; Cell Line; Colonic Neoplasms; DNA, Neoplasm; Dose-Response Relationship, Drug; Female; Humans; Leucine; Linoleic Acids; Melanoma; Neoplasm Proteins; RNA, Neoplasm; Thymidine; Tritium; Tumor Cells, Cultured; Uridine

The human intestinal Caco-2 cell line, described as enterocyte-like in a number of studies, was examined for its ability to carry out the metabolism of vitamin A normally required in the absorptive process. Caco-2 cells contained cellular retinol-binding protein II, a protein which is abundant in human villus-associated enterocytes and may play an important role in the absorption of vitamin A. Microsomal preparations from Caco-2 cells contained retinal reductase, acyl-CoA-retinol acyltransferase (ARAT), and lecithin-retinol acyltransferase (LRAT) activities, which have previously been proposed to be involved in the metabolism of dietary vitamin A in the enterocyte. When intact Caco-2 cells were provided with beta-carotene, retinyl acetate, or retinol, synthesis of retinyl palmitoleate, oleate, palmitate, and small amounts of stearate resulted. However, exogenous retinyl palmitate or stearate was not used by Caco-2 cells as a source of retinol for ester synthesis. While there was a disproportionate synthesis of monoenoic fatty acid esters of retinol in Caco-2 cells compared to the retinyl esters typically found in human chylomicrons or the esters normally synthesized in rat intestine, the pattern was consistent with the substantial amount of unsaturated fatty acids, particularly 18:1 and 16:1, found in the sn-1 position of Caco-2 microsomal phosphatidylcholine, the fatty acyl donor for LRAT. Both ARAT and LRAT have been proposed to be responsible for retinyl ester synthesis in the enterocyte.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acyltransferases; Adenocarcinoma; Alcohol Oxidoreductases; beta Carotene; Carotenoids; Cell Line; Colonic Neoplasms; Cytosol; Humans; Kinetics; Microsomes; Retinol O-Fatty-Acyltransferase; Retinol-Binding Proteins; Retinol-Binding Proteins, Cellular; Vitamin A

Topics: Adult; Aged; Ascorbic Acid; beta Carotene; Bronchial Neoplasms; Carotenoids; Colonic Neoplasms; Humans; Lipids; Middle Aged; Neoplasms; Prospective Studies; Risk Factors; Stomach Neoplasms; Vitamin A; Vitamin E

Breath methane and hydrogen, plasma acetate, serum selenium, vitamin A and beta-carotene were measured in 47 patients from whom colonic polyps had been removed by endoscopic polypectomy between 3 months and 2 years previously. Patients were compared with 39 control subjects in whom no abnormality was detected during colonoscopy. The proportion of methane exhalers was significantly (p less than 0.0005) higher in patients after polypectomy (66.0%) than in controls (28.2%). Mean plasma acetate was lower (p less than 0.025) in post-polypectomy patients (70.5 microM) than in control subjects (97.1 microM) while breath hydrogen was similar in both groups. The serum concentrations of the antioxidants selenium and beta-carotene showed no differences between the groups whereas vitamin A was higher (p less than 0.01) in serum samples of patients after polypectomy than of controls. These findings indicate that the colonic environment in post-polypectomy patients exhibits certain characteristics which may be related to the formation of benign tumors and possibly colon cancer.

Topics: Acetates; Adult; Aged; Antioxidants; beta Carotene; Breath Tests; Carotenoids; Colonic Neoplasms; Female; Humans; Hydrogen; Intestinal Polyps; Male; Methane; Middle Aged; Selenium; Vitamin A

Topics: Aged; Ascorbic Acid; beta Carotene; Carotenoids; Colonic Neoplasms; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasms; Prospective Studies; Rectal Neoplasms; Smoking; Stomach Neoplasms; Switzerland; Vitamin A; Vitamin E

A study was undertaken to determine whether prediagnostic serum levels of retinol, beta-carotene, vitamin E, and selenium are lower in colon cancer cases compared with matched, population-based controls. Sera were available from 25,802 participants of a serum collection campaign conducted in Washington County, Maryland in 1974. The authors identified from these participants 72 white colon cancer cases, who were first diagnosed with colon cancer during 1975-1983, and 143 white, living, cancer-free controls, matched to cases on the basis of age, sex, month of serum collection, and enumeration in a 1975 private census of Washington County. The mean values of serum nutrients in cases and controls, respectively, were 59.1 micrograms/dl and 61.8 micrograms/dl for retinol (p = 0.22), 32.9 micrograms/dl and 34.4 micrograms/dl for beta carotene (p = 0.52), 1.17 mg/dl and 1.27 mg/dl for vitamin E (p = 0.10), and 11.0 micrograms/dl and 11.5 micrograms/dl for selenium (p = 0.07). There were no consistent trends in the relative odds of colon cancer by quintiles of serum levels for any of the nutrients; however, a relative odds of 3.2 (95% confidence interval = 1.1-8.7) was found when persons in the four lowest quintiles of retinol were compared with those in the highest. No interactions with matching factors or between serum nutrients and no confounding effects of covariables were identified through conditional logistic regression analysis. The findings of this study do not support a strong association of low serum levels of retinol, beta-carotene, vitamin E, and selenium with an increased risk of subsequent colon cancer.

Topics: Adult; Aged; beta Carotene; Carotenoids; Colonic Neoplasms; Female; Humans; Male; Maryland; Middle Aged; Risk Factors; Selenium; Vitamin A; Vitamin E

The organospecific, 1,2-dimethylhydrazine-induced rat tumor model was used to test tumor formation in groups of animals receiving regular chow, powdered chow with 7%/wt ascorbic acid supplement, pelleted chow with 1%/wt beta-carotene supplement, and pelleted chow with placebo beadlets. Following a 16-week induction period, animals were killed and tumor formation was recorded. Tumor formation in the ascorbic acid supplement group was found to be significantly less than the control group. The beta-carotene group showed no difference in tumor formation compared with the placebo-beadlet control group. Tumor incidence was generally the same between the two control groups, and the ascorbic acid group had significantly fewer tumors than the beta-carotene group. In sum, ascorbic acid supplements in high doses significantly decreased tumor formation, whereas beta-carotene supplements in moderately high doses had no effect on tumor formation in this model.

Topics: 1,2-Dimethylhydrazine; Animals; Ascorbic Acid; beta Carotene; Body Weight; Carotenoids; Colonic Neoplasms; Diet; Dimethylhydrazines; Male; Rats; Rectal Neoplasms

Topics: Ascorbic Acid; beta Carotene; Blood Pressure; Body Composition; Carotenoids; Colonic Neoplasms; Diet; Female; Humans; Life Style; Lipids; Lung Neoplasms; Male; Neoplasms; Prospective Studies; Risk; Smoking; Stomach Neoplasms; Vitamin B Complex; Vitamin E; Vitamins