US EPA

2140403 

Journal Article 

Breast Cancer Chemoprevention With The Polyphenol Resveratrol 

Whitsett, TG; Lamartiniere, CA 

2005 

1 

Toxicological Sciences
ISSN: 1096-6080
EISSN: 1096-0929 

TOX/5001626 

84 

1-S 

English 

Even with the advent of new and aggressive therapeutics, breast cancer remains a destructive disease and a leading killer among cancers. In the US alone, there are more than 215, 000 new cases expected this year. There is, and should be, a concerted effort to prevent breast cancer. One polyphenol that has received much attention for health benefits is resveratrol, a polyphenolic phytoalexin found in red grapes (red wine). We have investigated the chemopreventive properties of resveratrol using the dimethylbenz(a)anthracene (DMBA) model for mammary carcinoma in the female Sprague-Dawley rat. Dietary administration of pure resveratrol (1g/kg AIN-76A diet) was provided, starting at parturition. Control animals were fed the phytoestrogen-free diet, AIN-76A. This dose of resveratrol resulted in a serum concentration of 2 +/- 0.64 uM. With at least 30 animals per group, tumor multiplicity, and latency were observed. Rats exposed to resveratrol via the diet showed a decrease in tumor multiplicity and had a longer latency as compared to control animals. Resveratrol in the diet resulted in no significant effect on body and uterine weights in 21 and 50 day old rats. In the uteri of 50 day old rats treated with resveratrol, we saw a decrease in protein levels of the steroid receptor coactivators: SRC-1, GRIP-1, and AIB1. While these coactivators are reported to increase the transcriptional activity of steroid receptors including estrogen, progesterone, and androgen receptors, resveratrol may attenuate sex steroid action by down-regulating their concentrations. The elucidation of the mechanisms for the preventive effects that we observe following polyphenol treatment will hopefully pave the way for clinical trials and the prevention of breast cancer.