Treatment based on 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 the study published in the Journal of Nutritional Biochemistry indicate that resveratrol is the most likely candidate of the phytoestrogens to offer safer HRT and chemoprevention of breast cancer due to its oestrogenic activity and high antitumour activity.
Phytoestrogens are natural plant substances found in food that exert weak oestrogen-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.
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, the researchers 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-κB-dependent transcriptional activity in MCF-7 breast cancer cells.
They found that phytoestrogens, except for glycitein, significantly enhanced oestrogen-response-element-dependent transcriptional activity up to a level similar to that of 17β-estradiol (E2). E2 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 G1/S transition in cell cycle analysis, similar to E2. 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-κB-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) α silencing had no effect on these reductions. In contrast, in the absence of apoptosis-inducing stimuli, only resveratrol reduced the ratio, and ERα silencing abolished this reduction. Thus, resveratrol might be the most promising candidate for HRT and chemoprevention of breast cancer due to its oestrogenic activity and high antitumour activity.
- Sakamoto T, Horiguchi H, Oguma E, Kayama F.J Effects of diverse dietary phytoestrogens on cell growth, cell cycle and apoptosis in estrogen-receptor-positive breast cancer cells. Nutr Biochem. 2009 Oct 2. [Epub ahead of print] View Abstract
- M. Gina Glazier; Marjorie A. Bowman A Review of the Evidence for the Use of Phytoestrogens as a Replacement for Traditional Estrogen Replacement Therapy Arch Intern Med. 2001;161(9):1161-1172. View Abstract View Full Paper