Polyphenolic compounds present in the diet are bioactive molecules which elicit a wide range of response both in vivo and in vitro. The interaction of these agents with endogenous hormones can have a profound effect on target tissues and hence be important in cancer prevention. The increased intake of soyfoods has been associated with a lowered risk of hormone- dependent cancers. The chemopreventive properties of soyfoods have been attributed to its isoflavone components, genistein and daidzein. In earlier studies, we examined the effect of genistein on estrogen receptor (ER) mediated pathways in human breast cancer MCF-7 cells. Our studies demonstrated that genistein mediated an antiestrogenic response by downregulating the expression of ER mRNA. We then proceeded to examine the differential effects of daidzein and equol on MCF-7 cells. Daidzein can be metabolized to equol by the action of intestinal microbes in humans and about 30% of the population are equol producers. The physiological impact of this is not clear and hence we evaluated the differential response of MCF-7 to the addition of either of these compounds. Our results indicate that in short term treatments, equol is more antiestrogenic than daidzein. But long-term exposure of MCF-7 cells with either daidzein or equol results in a significant downregulation of ER mRNA. In addition to the studies looking at the ER mediated effects of dietary factors, we are also interested in the ER independent effects as well. We are also examining the effect of diet-derived agents on the expression of growth factors. TGF b plays a critical role in regulating epithelial cell growth and we have examined the effect of genistein on the expression of TGF b in both normal and malignant mammary epithelial cells. These studies will assist in elucidating the various pathways that are modulated by dietary agents.
