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Breast Cancer Chemoprevention with the Polyphenol Resveratrol

Whitsett, T. and Lamartineiere, C.A. Department of Pharmacology and Toxicology, UAB Comprehensive Cancer Center, University of Alabama at Birmingham

Even with the advent of new and aggressive therapeutics, breast cancer remains a destructive disease and a leading killer among cancers. There is and should be a concerted effort to prevent breast cancer. We have shown that the consumption of genistein, a major constituent of soy, in a prepubertal rat confers protection against chemically-induced mammary cancer.

Another polyphenol that has received much attention for health benefits is resveratrol, a component found in red grapes (red wine). We have investigated the chemopreventive properties of resveratrol using the DMBA model for mammary carcinoma in the Sprague-Dawley rat. Dietary administration of pure resveratroil (1 g/kg AIN-76A diet) was provided for the entirety of life. Control animals were maintained on AIN-76A diet, reportedly void of phytoestrogens. With a least 30 animals per treatment, tumor incidence, multiplicity, and latency were observed.

Rats exposed to resveratrol via the diet showed a decrease in tumor multiplicity and had a longer latency compared to control animals. As for mechanisms of action, resveratrol treated animals showed an increased number of mammary terminal end buds and lobules at 21 days of age, indicating increased cell proliferation and differentiation. In the uteri of animals treated with resveratrol, we saw a decrease in protein levels of the steroid receptor coactivators: SRC-1, GRIP-1, and AIB1.

These coactivators increase the transcriptional activity of host steroid receptors, including estrogen, progesterone, and androgen receptors, and others.

We have show that genistein treatment can regulate GRIP-1 protein levels in the rat mammary gland, with an increase in 21 days followed by a decrease at 50 days, a susceptible time to carcinogen exposure. 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.

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