期刊
EUROPEAN JOURNAL OF PHARMACOLOGY
卷 677, 期 1-3, 页码 39-46出版社
ELSEVIER
DOI: 10.1016/j.ejphar.2011.12.032
关键词
Genistein; 6-hydroxydopamine; Insulin-like growth factor I receptor; SK-N-SH cell
资金
- National Natural Science Foundation of China [30570573, 30971004]
- Natural Science Foundation of Shandong Province [Y2007D49]
- Qingdao Municipal Science and Technology Bureau [11-2-4-2-(23)-jch]
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. (C) 2011 Elsevier B.V. All rights reserved.
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