coumestrol and glycitein

Phytoestrogens have attracted attention as being safer alternatives to hormone replacement therapy (HRT) and as chemopreventive reagents for breast cancer because dietary soy isoflavone intake has been correlated with reduction in risk. To identify safe and effective phytoestrogen candidates for HRT and breast cancer prevention, we investigated the effects of daidzein, genistein, coumestrol, resveratrol and glycitein on cell growth, cell cycle, cyclin D1 expression, apoptosis, Bcl-2/Bax expression ratio and p53-dependent or NF-kappaB-dependent transcriptional activity in MCF-7 breast cancer cells. Phytoestrogens, except for glycitein, significantly enhanced estrogen-response-element-dependent transcriptional activity up to a level similar to that of 17beta-estradiol (E(2)). E(2) increased cell growth significantly, coumestrol increased cell growth moderately, and resveratrol and glycitein reduced cell growth. Phytoestrogens, except for glycitein, stimulated the promotion of cells to G(1)/S transition in cell cycle analysis, similar to E(2). This stimulation was accompanied by transient up-regulation of cyclin D1. While genistein, resveratrol and glycitein all increased apoptosis and reduced the Bcl-2/Bax ratio, resveratrol reduced this ratio more than either genistein or glycitein. Moreover, resveratrol significantly enhanced p53-dependent transcriptional activity, but slightly reduced NF-kappaB-dependent transcriptional activity. On knockdown analysis, genistein, resveratrol and glycitein all reduced the Bcl-2/Bax ratio in the presence of apoptosis-inducing stimuli, and estrogen receptor (ER) alpha silencing had no effect on these reductions. In contrast, in the absence of apoptosis-inducing stimuli, only resveratrol reduced the ratio, and ERalpha silencing abolished this reduction. Thus, resveratrol might be the most promising candidate for HRT and chemoprevention of breast cancer due to its estrogenic activity and high antitumor activity.

Topics: Apoptosis; bcl-2-Associated X Protein; Breast Neoplasms; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Coumestrol; Estradiol; Estrogen Receptor alpha; Female; Genistein; Humans; Isoflavones; Phytoestrogens; Proto-Oncogene Proteins c-bcl-2; Resveratrol; Stilbenes

Isoflavones are present in soybeans and its products in concentrations up to 300 mg/100 g, have estrogenic and antiestrogenic properties, and may be protective against hormone-related cancers. The purpose of this cross-sectional study was to investigate the association between urinary isoflavone excretion and self-reported soy intake. A total of 102 women of Caucasian, Native Hawaiian, Chinese, Japanese, and Filipino ancestry completed a dietary questionnaire for soy products consumed during the last year and during the 24-h period before urine collection. Overnight urine samples were analyzed for coumestrol and the soy isoflavones genistein, daidzein, and glycitein and their main human metabolites by reverse-phase high-pressure liquid chromatography. Soy protein and isoflavone intake (predominantly from tofu) were estimated using published nutritional databases. Wilcoxon's rank-sum test scores and Spearman rank correlation coefficients were computed. Japanese women excreted more daidzein, genistein, and glycitein than did Caucasian women, whereas Caucasian women excreted slightly more coumestrol. Soy intake differed significantly among ethnic groups. Dietary soy protein and isoflavone intakes during the previous 24 h were positively related to urinary isoflavone excretion [rs = 0.61 (P < 0.0001) and 0.62 (P < 0.0001), respectively]. Urinary excretion of isoflavones was also related to annual dietary soy protein and isoflavone intake [rs = 0.32 (P < 0.0012) and 0.31 (P < 0.0016), respectively]. The strong correlation between urinary isoflavone excretion and self-reported soy intake validates the dietary history questionnaire that is now used in a study exploring dietary risk factors for breast cancer.

Topics: Adult; Aged; Aged, 80 and over; China; Coumestrol; Cross-Sectional Studies; Female; Genistein; Glycine max; Hawaii; Humans; Isoflavones; Japan; Middle Aged; Philippines; White People