phytoestrogens and Carcinoma

Epidemiologic studies suggest that nutritional phytoestrogens contained in soy are causally related to protection against hormone-dependent cancers. The incidence of colorectal cancer is at least 30% lower in women than in men in the United States. This suggests that estrogen and, conceivably, nutritional phytoestrogens are protective compounds against colorectal cancer for both sexes. Prevention of colorectal, mammary, and prostate cancer may also depend on optimal synthesis of the antimitotic prodifferentiating vitamin D hormonal metabolite 1,25-(OH)(2)-cholecalciferol (1,25-D3). Cytochrome-P450-hydroxylases responsible for synthesis (CYP27B1; 25-D3-1 alpha-hydroxylase) and catabolism (CYP24; 1,25-D3-24-hydroxylase) of 1,25-D3 are not only present in the kidney but are also expressed in human colonocytes, prostate cells, and mammary cells. In addition, levels of CYP27B1, vitamin D receptor, and estrogen receptor-beta (the high-affinity receptor for phytoestrogens) are enhanced early during human colorectal cancer, which suggests an interactive physiological defense against tumor progression. We demonstrate in human mammary and prostate cells concentration-dependent regulation of CYP27B1 and of CYP24 by genistein at 0.05-50 micromol/L. The high concentration of 50 micromol/L is very effective in eliminating CYP24 expression in prostate cancer cells. This high concentration can be achieved in vivo in the prostate by an as-yet-unknown concentrative mechanism. Soy feeding, or more effectively genistein feeding, elevates CYP27B1 and reduces CYP24 expression in the mouse colon. In mice fed low nutritional calcium, CYP24 rises in parallel to enhanced colonic proliferation, and genistein counteracts both. We suggest that nutritional soy or genistein can optimize extrarenal 1,25-D3 synthesis, which could result in growth control and, conceivably, in inhibition of tumor progression.

Topics: Animals; Breast Neoplasms; Carcinoma; Colorectal Neoplasms; Diet; Female; Humans; Isoflavones; Male; Phytoestrogens; Plant Preparations; Prostatic Neoplasms; Vitamin D

Topics: Alcohol Drinking; Breast Neoplasms; Carcinogens; Carcinoma; Diet; Dietary Fats; Estrogens, Non-Steroidal; Ethnicity; Fatty Acids; Feeding Behavior; Female; Fruit; Humans; Isoflavones; Meat; Phytoestrogens; Plant Preparations; Plants; Racial Groups; Risk Factors; Vegetables

Phytoestrogens are structurally similar to estrogens and may affect breast cancer risk by mimicking estrogenic/antiestrogenic properties. In Western societies, whole grains and possibly soy foods are rich sources of phytoestrogens. A population-based case-control study in German postmenopausal women was used to evaluate the association of phytoestrogen-rich foods and dietary lignans with breast cancer risk. Dietary data were collected from 2,884 cases and 5,509 controls using a validated food-frequency questionnaire, which included additional questions phytoestrogen-rich foods. Associations were assessed using conditional logistic regression. All analyses were adjusted for relevant risk and confounding factors. Polytomous logistic regression analysis was performed to evaluate the associations by estrogen receptor (ER) status. High and low consumption of soybeans as well as of sunflower and pumpkin seeds were associated with significantly reduced breast cancer risk compared to no consumption (OR = 0.83, 95% CI = 0.70-0.97; and OR = 0.66, 95% CI = 0.77-0.97, respectively). The observed associations were not differential by ER status. No statistically significant associations were found for dietary intake of plant lignans, fiber, or the calculated enterolignans. Our results provide evidence for a reduced postmenopausal breast cancer risk associated with increased consumption of sunflower and pumpkin seeds and soybeans.

Topics: 4-Butyrolactone; Aged; Breast Neoplasms; Carcinoma; Case-Control Studies; Cucurbita; Diet; Dietary Fiber; Female; Germany; Glycine max; Helianthus; Humans; Lignans; Middle Aged; Phytoestrogens; Postmenopause; Risk; Seeds

Phytooestrogens are known to cause anti-cancer effects on mamma carcinoma cells. In this study, the effects of the lignan secoisolariciresinol and the isoflavone glycosides and aglycones genistein, genistin, daidzein and daidzin were tested on MCF-7 and BT20 cells in vitro.. First, the cellular expression of hormone receptors was examined by immunohistochemical procedures. The effects of the phytooestrogens on the cells were detected by using three different assays measuring cell letality, viability and proliferation. The phytooestrogens were tested in concentrations of 1, 5, 10 and 50 μg/mL, respectively. 17β-oestradiol and tamoxifen were used as controls, respectively, in the same concentrations as the phytooestrogens.. The immunohistochemistry showed evidence of oestrogen- and progesterone receptors at the MCF-7 cell line, whereas no expression could be seen at the BT20 cells. Among the phytooestrogens, genistein and secoisolariciresinol showed various anti-cancerogenic effects on both cell lines, respectively, but only in the highest concentration. Regarding the controls, tamoxifen showed a stronger antivital and anti-proliferative effect on BT20 than on MCF-7. Oestradiol caused sporadic anti-cancer effects on both cell lines, respectively, at its highest concentration.. Genistein and Secoisolariciresinol have anti-cancer properties on MCF-7 and BT20 in vitro. There are differences in the effects of isoflavones depending on the glycolysation status. The role of the oestrogen receptors in the mechanisms of action of both the phytooestrogens and controls is of less importance. Further investigations have to be carried out, especially concerning the mechanisms of action. Phytooestrogens may be potential substances in the therapy of mamma carcinomas.

Topics: Breast Neoplasms; Butylene Glycols; Carcinoma; Cell Line, Tumor; Cell Proliferation; Cell Survival; Female; Genistein; Humans; Immunohistochemistry; Isoflavones; L-Lactate Dehydrogenase; Lignans; Phytoestrogens; Receptors, Estrogen; Receptors, Progesterone

Although case-control studies support the idea that soy foods or isoflavone intake is associated with a decreased risk of lung cancer, little evidence is available from prospective cohort studies. Moreover, no prospective study has addressed this association in men.. We investigated the association between isoflavone intake and lung cancer incidence.. We conducted a population-based prospective cohort study in 36,177 men and 40,484 women aged 45-74 y with no history of cancer at baseline in 1995-1999. Participants responded to a validated questionnaire, which included 138 food items. We used Cox proportional hazards regression analysis to estimate the hazard ratios (HRs) and 95% CIs of lung cancer incidence according to isoflavone intake, which was estimated by genistein content from soy foods.. During 11 y (671,864 person-years) of follow-up, we documented 481 male and 178 female lung cancer cases. In men we found an inverse association between isoflavone intake and risk of lung cancer in never smokers (n = 13,051; multivariate HR in the highest compared with the lowest quartile of isoflavone intake: 0.43; 95% CI: 0.21, 0.90; P for trend = 0.024) but not in current or past smokers. A similar, nonsignificant inverse association was seen in never-smoking women (n = 38,211; HR: 0.67; 95% CI: 0.41, 1.10; P for trend = 0.135). We also tested effect modification by smoking status (P for interaction = 0.085 in men and 0.055 in men and women combined).. In a large-scale, population-based, prospective study in Japan, isoflavone intake was associated with a decreased risk of lung cancer in never smokers.

Topics: Aged; Carcinoma; Diet Surveys; Female; Food Analysis; Genistein; Glycine max; Humans; Isoflavones; Japan; Lung Neoplasms; Male; Middle Aged; Phytoestrogens; Plant Extracts; Proportional Hazards Models; Prospective Studies; Risk Factors; Sex Factors; Smoking; Soy Foods; Surveys and Questionnaires

We evaluated the relationship of spot urinary concentrations of phytoestrogens with total prostate cancer and tumor grade in a hospital-based case-control study in Jamaica. Urine samples were analyzed for genistein, daidzein, equol (isoflavones), and enterolactone (lignan) among newly diagnosed cases (n = 175) and controls (n = 194). Urinary concentrations of enterolactone (lignan) were higher among cases. There were no significant differences in median concentrations of isoflavone excretion. Compared with non-producers of equol (reference tertile), men who produced equol were at decreased risk of total prostate cancer (tertile 2: OR, 0.42; CI, 0.23-0.75) (tertile 3: OR, 0.48; CI, 0.26-0.87) (p (trend), 0.020) and high-grade disease (tertile 2: OR, 0.31; CI, 0.15-0.61) (tertile 3: OR, 0.29; CI, 0.13-0.60) (p (trend), 0.001). Higher concentrations of enterolactone were positively related to total prostate cancer (OR, 1.85; CI, 1.01-3.44; p (trend), 0.027) as well as high-grade disease (OR, 2.46; CI, 1.11-5.46; p (trend), 0.023). There were no associations between urinary excretion of genistein and daidzein with risk of prostate cancer. Producers of equol (isoflavone) may be at reduced risk of total- and high-grade prostate cancer whereas enterolactone may increase the likelihood of disease.

Topics: Aged; Carcinoma; Case-Control Studies; Equol; Genistein; Humans; Isoflavones; Jamaica; Lignans; Male; Middle Aged; Phytoestrogens; Prostatic Neoplasms; Risk

To determine whether drought-stress alters phytoestrogens in red clover and whether red clover in the diet influences sexual development in Japanese quail, we fed chicks diets containing irrigated or non-irrigated clover. Irrigation altered phytoestrogenic activity of red clover (determined using an in vitro bioassay), with extracts of irrigated clover diet containing more estrogenic activity than extracts of non-irrigated clover diet. Chick growth was negatively correlated with the amount of irrigated or non-irrigated clover in the diet. Dietary red clover also depressed both absolute and relative gonad weights; however, relative oviduct weight was increased by the irrigated diet. Diets did not affect serum vitellogenin. These results reveal a negative influence of drought-stress on phytoestrogenic potency of clover, and that red clover in the diet can inhibit avian growth and development independent of irrigation state. Thus, phytoestrogens may affect reproductive development in wild birds, and environmental stressors may influence levels of phytoestrogens in the field.

Topics: Animal Feed; Animals; Carcinoma; Cell Line, Tumor; Coturnix; Droughts; Female; Humans; Male; Organ Size; Ovarian Neoplasms; Ovary; Oviducts; Phytoestrogens; Plant Extracts; Testis; Transfection; Trifolium; Vitellogenins

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Anticarcinogenic Agents; Apoptosis; Carcinoma; Chemoprevention; Chickens; Disease Models, Animal; Drug Delivery Systems; Fatty Acids, Omega-3; Female; Humans; Mice; Neoplasm Proteins; Ovarian Neoplasms; Phytoestrogens; Progestins; Resveratrol; Retinoids; Stilbenes; Vitamin D

The effect of treating mammary tumor-bearing rats with 2-methoxyestradiol (2-MeE2) on the urinary excretion of 12 phytoestrogens was investigated and compared with the changes in urinary excretion of estradiol metabolites. Alterations of excretion were registered for isoflavonoids, lignans and coumestans. However, due to large variations statistical significant differences were found only for two lignans, i.e. significant increases of enterodiol and matairesinol. Since the single components of phytoestrogens showed diverse alterations, excretions were expressed also by the ratio of total isoflavonoids to total lignans and compared with the estrogen ratios 2-hydroxyestrone to 16alpha-hydroxyestrone and A-ring to D-ring metabolites. The ratio of isoflavonoids to lignans was consistently decreased, whereas both ratios of estradiol metabolites were highly increased. The latter effect is probably due to demethylation of 2-methoxyestrone resulting in high catechol estrogen levels in urine. These results suggest that the high levels of catechol estrogens, produced by 2-MeE2 treatment, may have influenced the urinary excretion pattern of phytoestrogens.

Topics: 2-Methoxyestradiol; Animals; Carcinoma; Coumestrol; Estradiol; Female; Isoflavones; Lignans; Mammary Neoplasms, Experimental; Methylnitrosourea; Phytoestrogens; Rats; Rats, Sprague-Dawley

Clinical intervention studies and experimental studies with lignan-rich diets suggest that lignans may have inhibitory effects on prostate cancer, but no clinical or experimental studies with purified lignans have been published. The purpose of this study was to investigate the effect of a plant lignan 7-hydroxymatairesinol (HMR) on LNCaP human prostate cancer xenografts in athymic mice. Athymic nude male mice were injected subcutaneously with LNCaP cells. Starting 3 days after tumor cell injections, a control diet or a control diet supplemented with 0.15% or 0.30% of HMR was administered to mice and the tumor take rate and growth was observed for 9 weeks. HMR diet inhibited the growth of LNCaP tumors. Mice treated with HMR had smaller tumor volume, lower tumor take rate, increased proportion of nongrowing tumors, and higher tumor cell apoptotic index compared with controls. Furthermore, the cell proliferation index was reduced in mice receiving the 0.30% HMR diet compared with mice receiving the control diet. Our results suggest that dietary HMR started at the early phase of the tumor development inhibits the growth of the LNCaP human prostate cancer xenografts in athymic male mice.

Topics: Animals; Anticarcinogenic Agents; Apoptosis; Carcinoma; Cell Proliferation; Diet; Disease Models, Animal; Humans; Isoflavones; Lignans; Male; Mice; Mice, Nude; Models, Biological; Neoplasm Transplantation; Phytoestrogens; Prostate-Specific Antigen; Prostatic Neoplasms; Time Factors; Tumor Cells, Cultured; Xenograft Model Antitumor Assays

Environmental exposures, timing and duration of exposure, and one's genetic susceptibility all contribute to breast carcinoma and its progression. The purpose of this article was to identify known and suspected environmental causes of breast carcinoma, identify some environmental risk factors that may represent significant risk factors for certain groups, and describe current studies, supported by the National Institutes of Health/National Institute of Environmental Health Sciences, that clarify how environmental factors contribute to the development of breast carcinoma. Known and suspected environmental risk factors include organochlorine pesticides and other synthetic chemicals, hormonal factors (including exogenous endocrine disrupters), diet, tobacco and alcohol use, radiation, and magnetic fields. In at least 50% of breast carcinoma cases, none of the known risk factors apply. It is likely that an environmental component accounts for much of the unknown 50% of risk. Knowing the environmental factors for breast carcinoma development is an area that should be investigated intensely because it offers our best hope for prevention. Understanding why African-American women have a more aggressive form of breast carcinoma, whether they receive adequate follow-up treatment, and how these factors contribute to increased mortality rates requires further exploration. Data that demonstrate the lower incidence rate of breast carcinoma in Asian women, the relation to low fat diets and diets high in phytoestrogens, and how this might serve as a model for all women should be investigated. Finally, differences in behavioral and cultural attitudes, ethnicity, economic status, and life-style influences among different groups of women require further study to determine how these factors contribute to enhancing or reducing breast carcinoma risk.

Topics: Alcohol Drinking; Attitude to Health; Breast Neoplasms; Carcinogens; Carcinoma; Culture; Diet; Diet, Fat-Restricted; Environmental Exposure; Estrogens, Non-Steroidal; Ethnicity; Female; Follow-Up Studies; Health Behavior; Hormones; Humans; Isoflavones; Life Style; Magnetics; Neoplasms, Radiation-Induced; Pesticides; Phytoestrogens; Plant Preparations; Plants; Racial Groups; Research; Risk Factors; Smoking; Social Class; Survival Rate

The author is a former state legislator and feminist activist. Having traveled extensively in Asia, she questions the comparison of U.S. statistics regarding dietary/nutritional risk factors with those from countries whose public health standards are below that of the U.S. The author also notes that only recently has the U.S. had a critical mass of women in Congress that led to the funding of the first Women's Health Initiative. Countries in Asia have few women in positions of political power to advocate for public policies regarding women's health issues, especially concerning the gathering of data regarding breast carcinoma, which is considered a culturally sensitive topic. Although soy is considered a healthy staple of the majority of Asian diets because of its phytoestrogens, there is a mixed message to American consumers because cancer, rather than heart disease, is the leading cause of death among Asian females.

Topics: Asia; Breast Neoplasms; Carcinoma; Consumer Advocacy; Culture; Diet; Estrogens, Non-Steroidal; Ethnicity; Female; Health Promotion; Humans; Isoflavones; Nutritional Physiological Phenomena; Phytoestrogens; Plant Preparations; Plants; Public Policy; Racial Groups; Risk Factors; United States; Women's Health