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PubMed2006

Resveratrol, but not EGCG, in the diet suppresses DMBA-induced mammary cancer in rats.

Despite the advent of new and aggressive therapeutics, breast cancer remains a leading killer among women; hence there is a need for the prevention of this disease. Several naturally occurring polyphenols have received much attention for their health benefits, including anti-carcinogenic properties. Two of these are resveratrol, a component of red grapes, and epigallocatechin-3-gallate (EGCG), the major catechin found in green tea. In this study, we tested the hypothesis that these two polyphenols protect against chemically-induced mammary cancer by modulating mammary gland architecture, cell proliferation, and apoptosis. Female Sprague-Dawley CD rats were exposed to either resveratrol (1 g/kg AIN-76A diet), EGCG (0.065% in the drinking water), or control diet (AIN-76A) for the entirety of their life starting at birth. At 50 days postpartum, rats were treated with 60 mg dimethylbenz[a]anthracene (DMBA)/kg body weight to induce mammary cancer. Resveratrol, but not EGCG, suppressed mammary carcinogenesis (fewer tumors per rat and longer tumor latency). Analysis of mammary whole mounts from 50-day-old rats revealed that resveratrol, but not EGCG, treatment resulted in more differentiated lobular structures. Bromodeoxyuridine (BrdU) incorporation studies showed that resveratrol treatment caused a significant reduction in proliferative cells in mammary terminal ductal structures at 50 days postpartum, making them less susceptible to carcinogen insult. The epithelial cells of terminal end buds in the mammary glands of resveratrol-treated rats also showed an increase in apoptotic cells compared to the control or EGCG-treated rats as measured by a DNA fragmentation assay. At the given doses, resveratrol treatment resulted in a serum resveratrol concentration of 2.00 microM, while treatment with EGCG resulted in a serum EGCG concentration of 31.06 nM. 17beta-Estradiol, progesterone, and prolactin concentrations in the serum were not significantly affected by resveratrol or EGCG. Neither polyphenol treatment resulted in toxicity as tested by alterations in body weights, diet and drink consumptions, and day to vaginal opening. We conclude that resveratrol in the diet can reduce susceptibility to mammary cancer, while EGCG in the drinking water at the dose used was not effective.

Journal Article↗
PubMed2006

Inhibition of adenoma progression to adenocarcinoma in a 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced lung tumorigenesis model in A/J mice by tea polyphenols and caffeine.

The present study investigated the inhibitory effects of Polyphenon E [a standardized green tea polyphenol preparation containing 65% (-)-epigallocatechin-3-gallate] and caffeine on 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung tumor progression from adenoma to adenocarcinoma. Female A/J mice were treated with a single dose of NNK (103 mg/kg body weight, i.p.) and kept for 20 weeks for the mice to develop lung adenomas. The mice were then given a solution of 0.5% Polyphenon E or 0.044% caffeine as the sole source of drinking fluid until week 52. Both treatments significantly decreased the number of visible lung tumors. Histopathologic analysis indicated that Polyphenon E administration significantly reduced the incidence (by 52%) and multiplicity (by 63%) of lung adenocarcinoma. Caffeine also showed marginal inhibitory effects in incidence and multiplicity of adenocarcinoma (by 48% and 49%, respectively). Markers of cell proliferation, apoptosis, and related cell signaling were studied by immunohistochemistry, and the labeling index and staining intensity were quantified by the Image-Pro system. Polyphenon E and caffeine treatment inhibited cell proliferation (by 57% and 50%, respectively) in adenocarcinomas, enhanced apoptosis in adenocarcinomas (by 2.6- and 4-fold, respectively) and adenomas (both by 2.5-fold), and lowered levels of c-Jun and extracellular signal-regulated kinase (Erk) 1/2 phosphorylation. In the normal lung tissues, neither agent had a significant effect on cell proliferation or apoptosis. The results show that tea polyphenols (and perhaps caffeine) inhibit the progression of NNK-induced lung adenoma to adenocarcinoma. This effect is closely associated with decreased cell proliferation, enhanced apoptosis, and lowered levels of c-Jun and Erk1/2 phosphorylation.

Adenocarcinoma↗
PubMed2007

Food groups and renal cell carcinoma: a case-control study from Italy.

Although nutrition and diet have been related to renal cell carcinoma (RCC), the role of specific foods or nutrients on this cancer is still controversial. We evaluated the relation between a wide range of foods and the risk of RCC in an Italian case-control study including 767 patients (494 men and 273 women) younger than 79 years with incident, histologically confirmed RCC, and 1,534 controls (988 men and 546 women) admitted to the same hospitals as cases for a wide spectrum of acute, non-neoplastic conditions, not related to long term diet modifications. A validated and reproducible food frequency questionnaire, including 78 foods and beverages, plus a separate section on alcohol drinking, was used to assess patients' dietary habits 2 years before diagnosis or hospital admission. Multivariate odds ratios (OR) were obtained after allowance for energy intake and other major confounding factors. A significant direct trend in risk was found for bread (OR = 1.94 for the highest versus the lowest intake quintile), and a modest excess of risk was observed for pasta and rice (OR = 1.29), and milk and yoghurt (OR = 1.27). Poultry (OR = 0.74), processed meat (OR = 0.64) and vegetables (OR = 0.65) were inversely associated with RCC risk. No relation was found for coffee and tea, soups, eggs, red meat, fish, cheese, pulses, potatoes, fruits, desserts and sugars. The results of this study provide further indications on dietary correlates of RCC, and in particular indicate that a diet rich in refined cereals and poor in vegetables may have an unfavorable role on RCC.

Aged↗
PubMed1998

Cruciferous vegetables in relation to renal cell carcinoma.

Little is known about the possible role of diet in the development of renal cell carcinoma (RCC). A population-based case-control study was conducted in non-Asians of Los Angeles; it included 1,204 RCC patients and an equal number of neighborhood controls matched to the index cases by sex, date of birth (within 5 years) and ethnicity. Information on intake frequencies of food groups rich in vitamins A and C, various carotenoids and nitrosamines or their precursors was collected through in-person, structured interviews. After adjustment for non-dietary risk factors including level of education, obesity, history of hypertension, cigarette smoking and regular use of analgesics and amphetamines, there were strong inverse associations between cruciferous and dark green vegetable intakes and RCC risk (both p values for linear trend < 0.001). In terms of nutrients, there were significant inverse associations of RCC risk with consumption of a variety of carotenoids including alpha-carotene (p < 0.001), beta-carotene (p = 0.004), beta-cryptoxanthin (p = 0.01) and lutein (p = 0.005). However, after adjustment for these nutrients, we still observed a significant residual effect of cruciferous vegetables, suggesting that other substances present in these vegetables may be responsible, at least partially, for the observed reduction in risk of RCC. Dietary nitrosamines and their precursors were not related to RCC risk.

Adult↗
PubMed1999

Chemopreventive activity of very low dose dietary tannic acid administration in hepatoma bearing C3H male mice.

Tannins are plant polyphenols comprising a heterogeneous group of compounds. Tannic acid is a common tannin found in tea, coffee, immature fruits, etc. and it has also been used as a food additive. An increasing body of experimental evidence supports the hypothesis that tannins exert anticarcinogenic activity in chemically induced cancers in animal models. In the present study, tannic acid was administered in very low doses in the drinking water of C3H male mice divided into three groups (75 mg/l, 150 mg/l and 300 mg/l). These animals carry a genetic defect and show a high incidence of spontaneous liver tumors (> 50%) at an age older than 12 months. The results showed a decrease in the overall incidence of hepatic neoplasms (adenomas plus carcinomas): 53.3% of animals in the control group developed hepatic neoplasms versus 33.3% in the group given a low dose of tannic acid, 26.6% in the group given a medium dose and 13.3% in the high dosage group. The difference was more pronounced in the animals with carcinomas: 4.44% of mice who received tannic acid developed carcinomas versus 33.3% of those in the control group. Tannic acid administration did not affect the PCNA labeling index of normal hepatocytes. It is concluded that tannic acid dietary intake in low doses can exert a strong dose-dependent chemoprotective activity against spontaneous hepatic neoplasm development in C3H male mice, most probably through antipromoting mechanisms.

Adenoma↗
PubMed2004

Diet, anthropometric measures and prostate cancer risk: a review of prospective cohort and intervention studies.

We reviewed 37 prospective cohort and four intervention studies on potential dietary risk factors for prostate cancer, published between 1966 and September 2003. Some studies were limited by small size, crude measurement of dietary exposure and limited control for confounders. Intervention and prospective cohort studies support a protective role against prostate cancer for selenium, and possibly for vitamin E, pulses and tomatoes/lycopene. Overall consumption of meat, eggs, vegetables, fruit, coffee, tea, carotenoids and vitamins A, C and D was not consistently related to prostate cancer risk. Intervention studies also indicate that supplementation with beta-carotene does not lower prostate cancer risk, except possibly in men with low beta-carotene status at baseline. For specific types of meat, alcoholic drinks, dairy products, fat and anthropometric measures, most cohort studies suggest either an increased risk or no relation with prostate cancer. For calcium, two cohort studies suggest an increased risk at very high calcium intakes (>2000 mg/day). In conclusion, prospective studies are consistent with a protective role for selenium, and possibly vitamin E, pulses and tomatoes/lycopene, in the aetiology of prostate cancer. Studies are inconclusive on the role of meat, dairy products, fat, vegetables, fruits, alcohol and anthropometric measures, whereas a very high calcium intake appears to be positively associated with prostate cancer risk.

Anthropometry↗
PubMed2005

Inhibition of intestinal tumorigenesis in Apcmin/+ mice by (-)-epigallocatechin-3-gallate, the major catechin in green tea.

The present study was designed to investigate the effects of two main constituents of green tea, (-)-epigallocatechin-3-gallate (EGCG) and caffeine, on intestinal tumorigenesis in Apc(min/+) mice, a recognized mouse model for human intestinal cancer, and to elucidate possible mechanisms involved in the inhibitory action of the active constituent. We found that p.o. administration of EGCG at doses of 0.08% or 0.16% in drinking fluid significantly decreased small intestinal tumor formation by 37% or 47%, respectively, whereas caffeine at a dose of 0.044% in drinking fluid had no inhibitory activity against intestinal tumorigenesis. In another experiment, small intestinal tumorigenesis was inhibited in a dose-dependent manner by p.o. administration of EGCG in a dose range of 0.02% to 0.32%. P.o. administration of EGCG resulted in increased levels of E-cadherin and decreased levels of nuclear beta-catenin, c-Myc, phospho-Akt, and phospho-extracellular signal-regulated kinase 1/2 (ERK1/2) in small intestinal tumors. Treatment of HT29 human colon cancer cells with EGCG (12.5 or 20 micromol/L at different times) also increased protein levels of E-cadherin by 27% to 58%, induced the translocation of beta-catenin from nucleus to cytoplasm and plasma membrane, and decreased c-Myc and cyclin D1 (20 micromol/L EGCG for 24 hours). These results indicate that EGCG effectively inhibited intestinal tumorigenesis in Apc(min/+) mice, possibly through the attenuation of the carcinogenic events, which include aberrant nuclear beta-catenin and activated Akt and ERK signaling.

Animals↗
PubMed2005

Prognostic significance of metastasis-associated protein S100A4 (Mts1) in prostate cancer progression and chemoprevention regimens in an autochthonous mouse model.

PURPOSE: We recently showed that metastasis-promoting Mts1 gene (S100A4) and protein is overexpressed during progression of prostate cancer in humans. The purpose of this study was to assess the expression of S100A4 during autochthonous prostate cancer progression in transgenic adenocarcinoma of the mouse prostate (TRAMP) model. Because oral consumption of green tea polyphenols (GTP) has been shown to inhibit metastasis and prostate cancer in TRAMP, we further assessed the significance of S100A4 during chemoprevention regimen. EXPERIMENTAL DESIGN: Male TRAMP mice 8 weeks of age were equally divided into two groups. A freshly prepared 0.1% GTP solution in tap water was supplied thrice a week to experimental animals as the sole source of drinking fluid for 24 weeks, whereas the control group of animals received the same tap water throughout the experiment. The animals were sacrificed at 0, 8, 16, and 24 weeks of GTP feeding and were analyzed for S100A4 and E-cadherin. Additional untreated and treated nontransgenic controls were also included in the study. RESULTS: With the progression of age and prostate cancer growth in TRAMP mice, an increase in the expression of S100A4 at mRNA and protein level in dorsolateral prostate, but not in nontransgenic mice, occurred. GTP feeding to TRAMP mice resulted in marked inhibition of prostate cancer progression, which was associated with reduction of S100A4 and restoration of E-cadherin. CONCLUSIONS: S100A4 represents a promising marker for prostate cancer progression and could be employed as a biomarker in chemoprevention regimens.

Administration, Oral↗
PubMed1993

Protection against 12-O-tetradecanoylphorbol-13-acetate-caused inflammation in SENCAR mouse ear skin by polyphenolic fraction isolated from green tea.

Earlier studies conducted in our laboratory have shown that a polyphenolic fraction isolated from green tea (GTP) possesses anti-skin tumor initiating and anti-skin tumor promoting activity in the two-stage skin tumorigenesis protocol in SENCAR mouse. We have also shown that topical application of GTP inhibits tumor promoter-caused induction of epidermal ornithine decarboxylase activity in SENCAR mice in a dose-dependent manner, and that its oral feeding in drinking water to SKH-1 hairless mice enhances antioxidant and phase II enzyme activity in liver, lung, small bowel and skin. In this study, we show that single or multiple applications of GTP on SENCAR mouse ear prior to or after the application of 12-O-tetradecanoylphorbol-13-acetate (TPA) afford significant protection (P < 0.05) against TPA-induced edema. Pre-application of GTP also afforded significant protection against TPA-induced hyperplasia in the ear skin. The percentage protection by GTP both in terms of epidermal thickness and vertical cell layers was 75 and 90% respectively (P < 0.005). In further studies, we assessed the protective effect of GTP against TPA-caused infiltration of neutrophils in the ear skin of SENCAR mouse, by determining a naturally occurring constituent of neutrophils, myeloperoxidase, as a quantitative marker of tissue neutrophil content. Prior application of GTP resulted in significant protection against TPA-caused infiltration of neutrophils (P < 0.005). These results suggest that GTP possesses potential as a cancer chemopreventive agent against stage I tumor promotion.

Animals↗
PubMed1985

Breast cancer and the consumption of coffee.

The hypothesis has been raised that coffee consumption may increase the incidence of breast cancer, based on the report that fibrocystic breast disease, a risk factor for breast cancer, regresses after abstention from coffee and other methylxanthines. The relation between recent coffee consumption and the risk of breast cancer was evaluated in a case-control study, based on interviews conducted 1975-1982 at several mainly eastern US teaching and community hospitals. The responses of 2,651 women with newly diagnosed breast cancer were compared with those of 1,501 controls with nonmalignant conditions and 385 controls with cancers at other sites. The relative risk estimates for levels of coffee drinking up to seven or more cups daily, relative to none, approximated 1.0 with narrow 95% confidence intervals. After allowance for confounding, the relative risk estimate for drinking at least five cups a day was 1.2 (95% confidence interval, 0.9-1.6) using the noncancer controls and 1.1 (0.7-1.6) using the cancer controls. Coffee consumption was not associated with an increase in the risk of breast cancer among women with a history of fibrocystic breast disease, nor were tea or decaffeinated coffee associated with an increase in the risk of breast cancer. The results suggest that the recent consumption of coffee does not influence the incidence of breast cancer.

Adult↗
PubMed2006

Fruit and vegetable juices and Alzheimer's disease: the Kame Project.

BACKGROUND: Growing evidence suggests that oxidative damage caused by the beta-amyloid peptide in the pathogenesis of Alzheimer's disease may be hydrogen peroxide mediated. Many polyphenols, the most abundant dietary antioxidants, possess stronger neuroprotection against hydrogen peroxide than antioxidant vitamins. METHODS: We tested whether consumption of fruit and vegetable juices, containing a high concentration of polyphenols, decreases the risk of incident probable Alzheimer's disease in the Kame Project cohort, a population-based prospective study of 1836 Japanese Americans in King County, Washington, who were dementia-free at baseline (1992-1994) and were followed through 2001. RESULTS: After adjustment for potential confounders, the hazard ratio for probable Alzheimer's disease was 0.24 (95% confidence interval [CI], 0.09-0.61) comparing subjects who drank juices at least 3 times per week with those who drank less often than once per week with a hazard ratio of 0.84 (95% CI, 0.31-2.29) for those drinking juices 1 to 2 times per week (P for trend < .01). This inverse association tended to be more pronounced among those with an apolipoprotein Eepsilon-4 allele and those who were not physically active. Conversely, no association was observed for dietary intake of vitamins E, C, or beta-carotene or tea consumption. CONCLUSIONS: Fruit and vegetable juices may play an important role in delaying the onset of Alzheimer's disease, particularly among those who are at high risk for the disease. These results may lead to a new avenue of inquiry in the prevention of Alzheimer's disease.

Aged↗
PubMed2001

Dental caries among 10- to 14-year-old children in Ugandan rural areas with 0.5 and 2.5 mg fluoride per liter in drinking water.

The purpose of this study was to report on dental caries among Ugandan children residing in rural areas with either a low or high fluoride concentration in the drinking water, and to assess factors associated with caries. A random sample of 481 children aged 10-14 years was selected from Mpondwe (n = 81) and Kyabayenze (n = 82) in the Kasese district with 0.5 mg and from Mutolere/Kagera (n = 163) and Kabindi (n = 155) in Kisoro with 2.5 mg fluoride/l in the drinking water. The children were examined for caries using the DMFT index as described by the World Health Organization in 1987. The mean DMFT was 0.34 in the whole material. In one low fluoride area, Kyabayenze, all children were caries-free compared to 75% to 86% in the other areas. In Kyabayenze, tea with sugar was taken significantly less frequently than in the other low-fluoride area. In the high-fluoride district, age and consumption of tea with sugar were positively and significantly correlated with caries. Multivariate analyses showed age to be the only significant risk indicator.

Adolescent↗
PubMed1991

Inhibition of azoxymethane-induced colon carcinogenesis in rat by green tea polyphenol fraction.

The effect of green tea polyphenol fraction (GTP) on azoxymethane(AOM)-induced colon carcinogenesis was investigated in male Fischer rats. The rats were given AOM (7.4 mg/kg body weight) s.c. once a week for 10 weeks. A week after the treatment, they were divided into three groups: AOM-control (26 rats), AOM-GTP1 (26 rats) and AOM-GTP2 (25 rats). AOM-GTP1 and AOM-GTP2 groups respectively received 0.01 and 0.1% GTP in drinking water from week 11 to 26. AOM-control group received tap water throughout this experiment. Autopsy on week 26 showed that tumor incidence and average numbers of tumors per rat in the AOM-GTP1 and AOM-GTP2 groups were significantly lower than those of the AOM-control group: 38.1% and 47.6% versus 77.3%; 0.6 and 0.7 versus 1.5. Thus, it was concluded that GTP inhibited the development of AOM-induced colon carcinogenesis. The inhibition by GTP did not show significant dose dependence.

Animals↗
PubMed1988

Coffee drinking and nonfatal myocardial infarction in men under 55 years of age.

The relation of coffee consumption to the risk of nonfatal first myocardial infarction in men under 55 years of age was assessed in a hospital-based case-control study conducted from 1980 to 1983 in hospitals in Massachusetts, Rhode Island, Connecticut, and New York: 1,873 men with first nonfatal myocardial infarctions were compared with 1,161 controls admitted for conditions unrelated to coffee ingestion. After allowance for major risk factors for myocardial infarction, the relative risk estimate for recent consumption of caffeine-containing coffee increased with increasing level of daily intake, from 1.4 for one to two cups per day to 1.6 for three to four cups, 1.8 for five to nine cups, and 2.9 for greater than or equal to 10 cups, relative to consumption of no coffee (p less than 0.001 for trend). The association was apparent in each age group and in both smokers and nonsmokers. For those who drank decaffeinated coffee only, on the basis of small numbers, there was a suggestion of an increased risk among men who had consumed at least five cups daily for less than five years but not among those who had drunk this amount for at least five years; whether the apparent association among the shorter-term drinkers was due to previous consumption of caffeine-containing coffee could not be determined. The findings suggest that caffeine-containing coffee increases the risk of myocardial infarction and that men who drink at least five cups daily may increase their risk by about twofold or more.

Adult↗
PubMed1994

Proportional hazards analysis of diarrhea due to enterotoxigenic Escherichia coli and breast feeding in a cohort of urban Mexican children.

Ninety-eight women-infant pairs were followed for up to 50 weeks in the northern part of Guadalajara, Mexico, from August 1986 to July 1987 as part of a community-based, prospective study of the relation between infant feeding patterns and enterotoxigenic Escherichia coli producing heat-labile toxin (LT-ETEC) diarrheal disease. Strictly formula-fed children had an incidence of diarrhea over three times that of strictly breast-fed infants and twice that of breast-fed and supplementally fed children. Strictly formula-fed infants colonized by LT-ETEC were symptomatic for diarrhea nearly three times as often as strictly breast-fed infants and twice as often as infants receiving a mixed diet. The fitting of parametric hazard models to durations until LT-ETEC colonization revealed that the hazard for the first colonization was time invariant. The hazard of diarrhea increased by 400-500% during the rainy season or among children 3 months of age or older who received avena, a barley drink. The best-fitting hazard models to durations until symptomatic expression of LT-ETEC infection all increased through time. This hazard was inversely impacted by the overall amount of LT-ETEC-specific, immunoglobulin A antibodies the infant received via the mother's breast milk and by the provision of traditional medicinal teas.

Bacterial Toxins↗
PubMed1992

Coffee consumption and the risk of cancer of the exocrine pancreas: a case-control study in a low-risk population.

Data from a population-based, case-control study of 149 cases of cancer of the exocrine pancreas (excluding insulinomas) and 363 controls were used to test the hypothesis that coffee consumption increased the risk of cancer of the exocrine pancreas. Because of the high mortality from cancer of the pancreas, all information was obtained from proxy respondents for cases and controls. Increased risk was present for coffee drinkers [odds ratio (OR) = 2.38], cigarette smokers (OR = 2.27), and alcohol users (OR = 1.60), but the effect for alcohol disappeared after adjustment for cigarette use. Risk increased with the amount of coffee drunk with an OR of 2.38 in the those having at least 50,000 lifetime cups. This gradient was present in both men and women, and in cigarette smokers and nonsmokers. Increased risk was present for users of regular and decaffeinated coffee, but the risk was higher for users of decaffeinated coffee than users of regular coffee. Cigarette smoking, after controlling for coffee consumption, was an independent risk factor for pancreatic cancer, with odds ratios in the heaviest smokers of 2.71 (95% confidence interval = 1.41-5.21.

Adult↗
PubMed1976

Independence of serum lipid levels and dietary habits. The Tecumseh study.

Serum cholesterol and triglyceride levels were correlated with dietary habits of 4,057 adult participants in a prospective epidemiologic survey of cardiovascular disease in Tecumseh, Mich. Frequency of consumption of 110 different food items was determined for each participant and average weekly consumption rates of foods high in fat, sugar, starch, and alcohol content were calculated. Frequency of consumption of these nutrients was then correlated with serum cholesterol and triglyceride levels of individual subjects. Serum cholesterol and triglyceride values were not positively correlated with selection of dietary constituents. Positive correlations between serum lipid levels and adiposity were statistically significant. These findings suggest that serum cholesterol and triglyceride levels among Americans are more dependent on degree of adiposity than on frequency of consumption of fat, sugar, starch, or alcohol.

Adult↗