International Journal of Biochemistry & Cell Biology, 2013, 45(9):2045–2051.

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

Mercedes Nadal-Serrano, Daniel Gabriel Pons, Jorge Sastre-Serra, et al

Grupo multidisciplinar de Oncología Traslacional, Institut Universitari d’Investigació en Ciències de la Salut (IUNICS), Universitat de les Illes Balears, E07122 Palma de Mallorca, Illes Balears, Spain

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

荷兰《国际生物化学与细胞生物学杂志》，2013年9月

在乳腺癌细胞中金雀异黄素根据 ERα/ERβ之比调节氧化应激性︰对 线粒体功能、 去乙酰化酶、 解偶联蛋白 2 和抗氧化酶的影响

梅赛德斯 圣诞 塞拉诺，丹尼尔 加布里埃 庞斯，豪尔赫  萨斯特雷 塞拉，等

西班牙巴利阿里群岛大学健康科学研究所(IUNICS) 平移肿瘤研究的多学科小组

金雀异黄素是一种具有生物活性与雌激素活性的大豆异黄酮，被发现存在于各种豆制品中。这种天然化合物表现出广泛的生物活性，但它最出名的能力是能够抑制癌症的进展，特别是类似乳腺癌的激素相关疾病。金雀异黄素已被证明绑定到雌激素受体 α （ERα） 和雌激素受体 β （ERβ），尽管它对ERβ有较高的亲和力。ERα/ ERβ 的比值是乳腺肿瘤预后的标志，并且ERβ 的表达可能表示肿瘤更良性的状态，而 ERα则 表示恶性肿瘤。本研究的目的是在乳腺癌细胞中通过与具有不同 ERα/ERβ 比率雌激素受体之间的相互作用，探讨金雀异黄素对氧化应激和线粒体功能的作用。较低的ERα/ERβ 比值的T47D 细胞表现出较低的氧化应激和较强的线粒体功能，伴随着解偶联蛋白 2 和去乙酰化酶的上调。另一方面，金雀异黄素治疗的细胞MCF-7，具有最高的 ERα/ERβ 比值，在可控情况下报道没有变化。