The Phytoestrogen Genistein Affects Breast Cancer Cells Treatment Depending on the ER alpha/ER beta Ratio

Genistein (GEN) is a phytoestrogen found in soybeans. GEN exerts its functions through its interaction with the estrogen receptors (ER), ER alpha and ER beta, and we previously reported that the ER alpha/ER beta ratio is an important factor to consider in GEN-treated breast cancer cells. The aim of this study was to investigate the effects of GEN in breast cancer cells with different ER alpha/ER beta ratio: MCF-7 (high ratio), T47D (low ratio), and MCF-7 overexpressing ER beta (MCF7 + ER beta) treated with cisplatin (CDDP), paclitaxel (PTX) or tamoxifen (TAM). Cell viability, ROS production, autophagy, apoptosis, antioxidant enzymes protein levels, and cell cycle were analyzed. GEN treatment provoked an increase in cell viability in MCF-7 cells and in the antioxidant enzymes protein levels in combination with the cytotoxic agents, decreasing ROS production (CDDP + GEN and TAM + GEN) and autophagy (TAM + GEN) or apoptosis (CDDP + GEN and TAM + GEN). Moreover GEN treatment enhanced the cell cycle S phase entry in CDDP | GEN- and TAM | GEN- treated MCF-7 cells and, in the case of CDDP + GEN, increased the proportion of cells in the G2/M phase and decreased it in the subG(0)/G(1) phase. Otherwise, in the T47D and MCF7 + ER beta cells the combination of GEN with cytotoxic treatments did not cause significant changes in these parameters, even TAM + GEN- treated T47D cells showed less cell viability due to an increment in the autophagy. In conclusion, GEN consumption may be counterproductive in those patients receiving anticancer treatment with a high ER alpha/ER beta ratio diagnosed breast cancer and it could be harmless or even beneficial in those patients with a lower ER alpha/ER beta ratio breast cancer cells. (C) 2015 Wiley Periodicals, Inc.