Soy Metabolites, Isoflavones in Cell Growth and Apoptosis
Annual rept. 13 Jun 1998-13 Jul 1999
WAYNE STATE UNIV DETROIT MI
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Epidemiological studies suggest that the phytochemicals, genistein and daidzein, are the anti-cancer agents found in Asian diets which contribute to a decreased breast cancer risk. In the current study, we investigated the molecular mechanism by which genistein inhibits cell growth and induces apoptosis. Our data show that genistein induces G2M cell cycle arrest, dose-dependent cell growth inhibition, down-regulation of Bcl-2 and cyclin B, and up-regulation of p21WAF-1 at low concentrations 15-30 micro-M in MCF-7, MDA-MB 231, MDA-MB 435 and erbB-2 transfected MDA-MB 435 clones of breast cancer cells. In contrast, the effect of genistein on MCF-10A normal breast epithelial cells was significantly different than breast cancer cells or MCF-10 Aneo T cells. The cell cycle arrest, cell growth inhibitory effect, and up-regulation of p21 were much more pronounced in MCF-10AneoT compared to MCF-10A cells, as previously reported. We also observed a down-regulation of cyclin B1 CycB1 in both cell lines, similar to that found in breast cancer cells. In addition, we could not find any evidence of apoptosis in genistein treated MCF-10A and MCF-10 Aneo T cells compared to breast cancer cells where apoptosis was observed. The significance of these results will further be explored by additional studies in the future.
- Medicine and Medical Research