Genistein modulates oxidative stress in breast cancer cell lines according to ERα/ERβ ratio: Effects on mitochondrial functionality, sirtuins, uncoupling protein 2 and antioxidant enzymes

Genistein is a biologically active isoflavone with estrogenic activity and can be found in a variety of soy products. This natural compound displays a wide array of biological activities, but it is best known for its ability to inhibit cancer progression, especially for hormone-related ones such as breast cancer. Genistein has been shown to bind both the estrogen receptor alpha (ER alpha) and the estrogen receptor beta (ER beta), although it has a higher affinity for the ER beta. The ER alpha/ER beta ratio is a prognostic marker for breast tumors, and ER beta expression could indicate the presence of tumors more benign in state, whereas ERa indicates malignant tumors. The objective of the present study was to investigate the effects of genistein on oxidative stress and mitochondrial functionality through its interaction with the estrogen receptor in breast cancer cell lines with different ER alpha/ER beta ratios. The lower ER alpha/ER beta ratio T47D cell line showed lower oxidative stress and greater mitochondrial functionality, along with an up-regulation of uncoupling protein 2 and sirtuins. On the other hand, genistein-treated MCF-7 cell line, with the highest ER alpha/ER beta ratio, reported no changes for the control situation. On the whole, our results show different genistein effects depending on ER alpha/ER beta ratio for oxidative stress regulation, mitochondrial functionality, and modulation of UCPs, antioxidant enzymes and sirtuins in breast cancer cell lines. Effects of genistein on oxidative stress and mitochondria could be due at least in part, to a higher ER beta presence, but could also be due to up-regulation of ER beta caused by the genistein treatment. (C) 2013 Elsevier Ltd. All rights reserved.