Treatment with resveratrol could be a safer alternative to hormone replacement therapy (HRT) in postmenopausal women and could help prevent breast cancer, according to a new study.
The findings of a study published in the Journal of Nutritional Biochemistry indicate that resveratrol is the most likely phytoestrogen to offer safer HRT and chemoprevention of breast cancer due to its estrogenic and high antitumor activity.
Phytoestrogens are natural plant substances found in food that exert weak estrogen-like activity toward mammals, such as daidzein, genistein and glycitein found in soybeans and soy products, coumestrol in mung bean and alfalfa sprouts and resveratrol in grape skins and red wine.
According to the authors, estrogens with or without progestin have been used for HRT in postmenopausal women, but they increase the risk of breast cancer, and they report that in recent years, phytoestrogen supplements such as extracts from soy and red clover have become attractive as safer alternatives, with their efficacy investigated in clinical trials.
The effects of phytoestrogens on cancer prevention are still controversial. Conflicting reports have clouded the picture about the beneficial effects of soy isoflavones, with some studies indicating that breast cancer cells in mice were stimulated by the isoflavones. But population studies have shown that women with a high-soy diet generally have lower rates of breast cancer.
The researchers said that the aim of this study was to assess the estrogen-like effects and antitumor effects of individual dietary phytoestrogens by analyzing their effects on tumor cell growth, cell cycle and apoptosis (programmed cell death).
“We also performed experiments with and without E2 (sex hormone estradiol) to simulate premenopausal or postmenopausal status and to acquire useful information for HRT in postmenopausal women and breast cancer prevention in premenopausal and postmenopausal women,” they reported.
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.
“Because it (resveratrol) stimulated the transcription of endogenous estrogen receptor (ER) and proapoptotic effects, this phytoestrogen is the most promising candidate as an HRT alternative and chemopreventive reagent for breast cancer,” they concluded.
The researchers added that their results indicated that daidzein causes a slight cell-stimulating effect in the absence of estradiol, which may lead to an increased risk of breast cancer in postmenopausal women taking supplements containing these phytoestrogens.
The authors said that further research is needed to understand the mechanism by which resveratrol represses cell growth.
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.
T Sakamoto, H Horiguchi, E Oguma, F Kayama. Effects of diverse dietary phytoestrogens on cell growth, cell cycle and apoptosis in estrogen-receptor-positive breast cancer cells. J. Nutr Biochem; Published online ahead of print: doi: 10.1016/j.jnutbio.2009.06.010