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

Abstract

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.

• Authors: Quan-Gui Gao, Jun-Xia Xie, Man-Sau Wong, Wen-Fang Chen
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 677 Issue 1-3 Pg. 39-46 (Feb 29 2012) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 22227334 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier B.V. All rights reserved.

Chemical References

• Estrogens
• Neuroprotective Agents
• Proto-Oncogene Proteins c-bcl-2
• Quinolizines
• bcl-2-Associated X Protein
• JB 1-0
• Oxidopamine
• Genistein
• Luciferases
• Receptor, IGF Type 1
• Mitogen-Activated Protein Kinases

Topics

• Cell Cycle (drug effects)
• Cell Death (drug effects)
• Cell Line, Tumor
• Dose-Response Relationship, Drug
• Estrogens (genetics)
• Genistein (antagonists & inhibitors, pharmacology)
• Humans
• Luciferases (genetics)
• Membrane Potential, Mitochondrial (drug effects)
• Mitogen-Activated Protein Kinases (metabolism)
• Neuroblastoma (pathology)
• Neurons (cytology, drug effects, metabolism)
• Neuroprotective Agents (pharmacology)
• Oxidopamine (toxicity)
• Phosphorylation (drug effects)
• Proto-Oncogene Proteins c-bcl-2 (genetics)
• Quinolizines (pharmacology)
• Receptor, IGF Type 1 (metabolism)
• Response Elements (genetics)
• Signal Transduction (drug effects)
• Up-Regulation (drug effects)
• bcl-2-Associated X Protein (genetics)