European Journal of Pharmacology, 2012, 677(1-3):39-46.

IGF-I receptor signaling pathway is involved in the neuroprotective effect of genistein in the neuroblastoma SK-N-SH cells

Quan Gui Gao, Jun Xia Xie, Man Sau Wong, et al

State Key Disciplines: Physiology (in incubation), Department of Physiology, Medical College of Qingdao University, Qingdao, PR China; Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong SAR, PR China

Genistein, an isoflavone naturally found in soy products, displays estrogenic properties. Our previous study clearly demonstrated that genistein can activate the insulin-like growth factor-I receptor (IGF-IR) signaling pathway in human breast cancer MCF-7 cells. The present study aims to test the hypothesis that the IGF-I receptor signaling pathway is involved in the neuroprotective effects of genistein in neuroblastoma SK-N-SH cells. Our results revealed that pretreatment with genistein resulted in an enhancement in the survival of human neuroblastoma SK-N-SH cells against 6-hydroxydopamine (6-OHDA)-induced neurotoxicity. 6-OHDA arrested the cells at G(0)G(1) phase and prevented S phase entry. Genistein pretreatment could reverse the cytostatic effect of 6-OHDA on cell cycle. The decreased mitochondrial membrane potential induced by 6-OHDA could be also reversed by genistein pretreatment. These effects could be completely blocked by co-treatment with JB-1, which is the specific antagonist of the IGF-I receptor. Furthermore, genistein pretreatment restored the 6-OHDA-induced up-regulation of Bax and down-regulation of Bcl-2 mRNA and protein expression. Genistein treatment alone could significantly increase the phosphorylation level of MEK and induce ERE luciferase activity. Co-treatment with IGF-I could enhance the effect of genistein on cell proliferation and MEK phosphorylation. This study provides the first evidence that genistein has neuroprotective effects against 6-OHDA-induced neurotoxicity in SK-N-SH cells and activation of the IGF-I receptor signaling pathway might be involved in actions of genistein.

荷兰《欧洲药理学杂志》，2012年2月

在神经母细胞瘤 SK-N-SH 细胞中胰岛素生长因子受体信号转导通路参与金雀异黄素的神经保护作用

高权贵，谢俊霞，黄文秀，等

中国青岛医科大学生物学院国家重点学科: （孵化） 生理学；中国香港特别行政区香港理工大学应用生物学和化学技术学院等

金雀异黄素，一种大豆中的天然异黄酮，表现出雌激素特性。我们前期的研究清楚地表明，在人体乳腺癌 MCF-7 细胞中金雀异黄素能激活胰岛素样生长因子-I受体（IGF-IR）信号转导通路。本研究的目的在于验证IGF-IR信号转导通路参与了金雀异黄素在神经母细胞瘤 SK-N-SH 细胞中的神经保护作用。我们的研究结果表明，用金雀异黄素预处理可以增强人体神经母细胞瘤 SK-N-SH 抗6-羟基多巴胺 （6-OHDA）诱导神经毒性的细胞存活率。6-OHDA在 G(0)G(1) 阶段中止细胞， 阻止进入S期。金雀异黄素预处理可能逆转6-OHDA对细胞周期的抑制细胞生长作用。金雀异黄素预处理，也能逆转6-OHDA降低的线粒体膜电位。这些作用可能被IGF-I的一种特殊拮抗剂JB-1的联合治疗完全阻滞。此外，金雀异黄素预处理恢复了6-OHDA诱导的Bax上调和Bcl-2 mRNA 与蛋白表达下调。单独的金雀异黄素治疗可以显著增加 MEK的 磷酸化水平并诱导 ERE 荧光素酶的活性。与IGF-I联合治疗可以提高金雀异黄素对细胞增殖和 MEK 磷酸化的作用。本研究提供了第一个证据，证明在SK- N- SH 细胞中金雀异黄素具有保护作用，对抗 6-OHDA诱导的神经毒性并且活化的IGF-IR信号转导通路可能参与了金雀异黄素的作用机制。