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2,3,4',5-Tetrahydroxystilbene-2-0-beta-D-glucoside inhibits platelet-derived growth factor-induced proliferation of vascular smooth muscle cells by regulating cell cycle.
MedLine Citation:
PMID:  21348889     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
2,3,4',5-Tetrahydroxystilbene-2-0-beta-D-glucoside (TSG) has been found to have an anti-atherosclerotic effect. Vascular smooth muscle cells (VSMCs) proliferation contributes to the pathobiology of atherosclerosis. The aim of this study was to investigate the effects of TSG on platelet derived growth factor (PDGF)-BB induced VSMCs proliferation and to explore the molecular mechanisms of such effects. Cultured rat VSMCs were pretreated with TSG (l-50 μmol/L) for 1 h, followed by exposure to PDGF-BB (10 ng/mL) for 24 h, after which cell proliferation and cell cycle was examined. The protein expression of cell cycle regulators including retinoblastoma (Rb), cyclin D1/E, cyclin-dependent kinase (CDK)2/4, CDK inhibitors p21 and p27, and proliferative cell nuclear antigen (PCNA) was examined. Furthermore, activation of extracellular signal-regulated kinase1/2 (ERK1/2) was determined to elucidate the possible upstream mechanism by which TSG affects cell cycle regulators. Our data indicate that TSG inhibited PDGF-BB induced VSMCs proliferation in a dose-dependent manner, possibly through its ability to block the progression of cell cycle from G1 to S phase. In addition, TSG significantly inhibited PDGF-BB induced phosphorylation of Rb and expression of cyclin D1, CDK4, cyclin E, CDK2, and PCNA. TSG also suppressed both PDGF-BB induced down-regulation of p27 and up-regulation of p21. Finally, TSG inhibited PDGF-BB-induced activation of ERK1/2. Together, our findings provide the first evidence that TSG could inhibit PDGF-BB stimulated VSMCs proliferation via cell cycle arrest in association with modulation of the expression of cell cycle regulators, which may be mediated, at least in part, by suppression of ERK1/2 activation.
Authors:
Xiao-Le Xu; Yan-Juan Huang; Yu-Qin Wang; Xiang-Fan Chen; Wei Zhang
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-2-23
Journal Detail:
Title:  Clinical and experimental pharmacology & physiology     Volume:  -     ISSN:  1440-1681     ISO Abbreviation:  -     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-2-25     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0425076     Medline TA:  Clin Exp Pharmacol Physiol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2011 Blackwell Publishing Asia Pty Ltd.
Affiliation:
Department of Pharmacology, Nantong University School of Medicine, Nantong, China.
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