Genistein in the control of breast cancer cell growth: insights into the mechanism of action in vitro

Genistein significantly inhibited cell growth (IC50 around 10 mu M) of MCF-7, MDAMB-231 and HBL-100 cell lines, but not of skin-derived fibroblasts and counteracted the growth-stimulatory effects exerted by estradiol and growth factors. It abolished the paracrine stimulation observed in MCF-7 cells in co-culture with MDAMB-231 or fibroblasts. Genistein-treated cells accumulated in the S and G(2)/M phases of the cell cycle and underwent apoptosis. Genistein decreased tyrosine phosphorylation induced upon treatment with transforming growth factor-alpha. Finally, genistein bound the estrogen receptor (ER) (relative affinity constant K-d = 4 nM), induced pS2 and cathepsin-D transcription and increased nuclear ER levels. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.