We have characterized the estrogenic/antiestrogenic activity of flavonoids, e.g. genistein, equol and daidzein in an in vitro model using MCF-7 cells. We have demonstrated that the above effects are mediated via the estrogen receptor (ER). We are presently examining the effects of curcumin, a polyphenolic pigment responsible for the yellow colour of curry. Our studies so far have shown that curcumin mediates its effects independent of the ER. It is possible that the estrogen-like effect of curcumin may be mediated via the epidermal growth factor receptor (EGFR). Hence, we are examining the effect of curcumin on EGFR mRNA expression in an EGFR overexpressing estrogen receptor negative cell line, MDA-MB 468. Transforming growth factors have been shown to play an important role in modulating breast cancer growth. Alterations in TGF b expression would have a significant effect on the proliferation of breast epithelial cells. We examined the effect of genistein on the expression of TGF beta1 mRNA in MCF-7 cells as well as in normal human mammary epithelial cells (HMEC). Our studies indicate that HMEC respond to the addition of genistein by an early increase in TGF beta1 mRNA expression. In the case of MCF-7, however, we did not observe any such effect. It is interesting that a dietary agent such as genistein is able to produce a specific response in normal but not in malignant mammary epithelial cells and we are investigating the cause for this differential effect.
