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

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• 作者：Mercedes Nadal-Serrano ; Daniel Gabriel Pons ; Jorge Sastre-Serra ; Ma del Mar Blanquer-Rossell¨® ; Pilar Roca ; Jordi Oliver
• 关键词：CAT ; catalase ; DCFDA ; 2&prime ; 7&prime ; -dichlorofluorescein diacetate ; ER¦Á ; estrogen receptor alpha ; ER¦Â ; estrogen receptor beta ; GEN ; genistein ; 4-HNE ; 4-hydroxy-2-nonenal ; MnSOD ; manganese superoxide dismutase ; ¦¤¦×m ; mitochondrial membrane potential
• 刊名：The International Journal of Biochemistry and Cell Biology
• 出版年：2013
• 出版时间：September, 2013
• 年：2013
• 卷：45
• 期：9
• 页码：2045-2051
• 全文大小：631 K

文摘

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¦Á) and the estrogen receptor beta (ER¦Â), although it has a higher affinity for the ER¦Â. The ER¦Á/ER¦Â ratio is a prognostic marker for breast tumors, and ER¦Â expression could indicate the presence of tumors more benign in state, whereas ER¦Á 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¦Á/ER¦Â ratios. The lower ER¦Á/ER¦Â 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¦Á/ER¦Â ratio, reported no changes for the control situation. On the whole, our results show different genistein effects depending on ER¦Á/ER¦Â 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¦Â presence, but could also be due to up-regulation of ER¦Â caused by the genistein treatment.