Document Detail


β-Sitosterol inhibits cell cycle progression of rat aortic smooth muscle cells through increases of p21cip1 protein.
MedLine Citation:
PMID:  20731356     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Abnormal proliferation of vascular smooth muscle cells (VSMCs) plays a central role in the pathogenesis of atherosclerosis. β-Sitosterol, an important phytosterol found in plant food, is known to exert antiatherosclerosis activity. However, the molecular mechanisms underlying β-sitosterol-induced antiproliferation of VSMCs were still not clear. This study demonstrated that β-sitosterol (1-20 μM) concentration-dependently inhibited proliferation of rat aortic smooth muscle cells (RASMCs) without cytotoxic effect. Flow cytometric analysis revealed that β-sitosterol arrested cell cycle progression through down-regulation of cyclin E and cyclin-dependent kinase (CDK)2 and up-regulation of p21cip1. In the β-sitosterol-treated RASMCs, the formation of the CDK2-p21cip1 complex was increased and the assayable CDK2 activity was decreased. Knockdown of the expression of p21cip1 gene prevented β-sitosterol-induced cell cycle arrest in RASMCs. In conclusion, β-sitosterol inhibited VSMC proliferation by increasing the levels of p21cip1 protein, which in turn inhibited the CDK2 activity, and finally interrupted the progress of the cell cycle.
Authors:
Ming-Hsien Chien; Tong-Sheng Lee; Yu-Chih Liang; Wen-Sen Lee
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of agricultural and food chemistry     Volume:  58     ISSN:  1520-5118     ISO Abbreviation:  J. Agric. Food Chem.     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-09-15     Completed Date:  2011-01-14     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0374755     Medline TA:  J Agric Food Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  10064-9     Citation Subset:  IM    
Affiliation:
Taipei Medical University-Wang-Fang Hospital, Taipei, Taiwan.
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MeSH Terms
Descriptor/Qualifier:
Animals
Aorta, Thoracic / cytology,  drug effects*,  metabolism
Atherosclerosis / prevention & control
Cell Cycle / drug effects*
Cell Proliferation / drug effects
Cells, Cultured
Cyclin-Dependent Kinase Inhibitor p21 / genetics,  metabolism*
Hypolipidemic Agents / adverse effects,  pharmacology*
Male
Muscle, Smooth, Vascular / cytology,  drug effects*,  metabolism
Rats
Rats, Sprague-Dawley
Sitosterols / adverse effects,  pharmacology*
Up-Regulation / drug effects*
Chemical
Reg. No./Substance:
0/Cdkn1a protein, rat; 0/Cyclin-Dependent Kinase Inhibitor p21; 0/Hypolipidemic Agents; 0/Sitosterols; 5779-62-4/sitosterol

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