Genistein Modulates Proliferation and Mitochondrial Functionality in Breast Cancer Cells Depending on ERalpha/ERbeta Ratio

Breast cancer is the most common malignancy in women of developed countries. The aim of this study was to investigate whether genistein, a soy phytoestrogen, and 17-estradiol (E2) could have effects on the cell cycle and mitochondrial function and dynamics. Three human breast cancer cell lines with different estrogen receptor alpha (ER) and estrogen receptor beta (ER) ratio were used: MCF-7 (high ER/ER ratio), T47D (low ER/ER ratio) and MDA-MB-231 (ER-negative). Cell proliferation, cell cycle, mitochondrial functionality, and mitochondrial dynamics parameters were analyzed. E2 and genistein treatment induced cell proliferation and apoptosis inhibition in MCF-7, but not in T47D and MDA-MB-231. Moreover, genistein treatment produced an up-regulation of ER and a rise in cytochrome c oxidase activity in T47D cells, decreasing the ATP synthase/cytochrome c oxidase ratio. Finally, genistein treatment produced a drop in mitochondrial dynamics only in MCF-7 cells. In summary, the beneficial effects of genistein consumption depend on the ER/ER ratio in breast cells. Therefore, genistein treatment produces cell cycle arrest and an improvement of mitochondrial functionality in T47D cells with a low ER/ER ratio, but not in MCF-7 (high ER/ER ratio) and MDA-MB-231 (ER-negative) ones. J. Cell. Biochem. 115: 949-958, 2014. (c) 2013 Wiley Periodicals, Inc.