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Simvastatin inhibits cell growth and induces apoptosis and G0/G1 cell cycle arrest in hepatic cancer cells.
MedLine Citation:
PMID:  20878096     Owner:  NLM     Status:  In-Process    
Hepatocellular carcinoma (HCC) is one of major health concerns worldwide and one of leading causes of cancer death after lung and gastric cancers. Simvastatin is a cholesterol-lowering drug which inhibits 3-hydroxy-3-methylglutarylcoenzyme CoA (HMG-CoA) reductase. Simvastatin exhibits numerous pleiotropic effects including anti-cancer activity. Yet, the anticancer effects in HCC remain poorly characterized. Therefore, in this study, we investigated the effects of simvastatin on tumor cell growth, apoptosis and cell cycle. HepG2 and Huh7 cell lines were treated with simvastatin (32 and 64 µM) for different time periods. Tumor cell growth was assessed using MTT assay. Apoptosis and cell cycle analysis were also evaluated. Analysis of cell cycle proteins involved in simvastatin-induced manipulation was performed by Western blot and quantitative RT-PCR analyses. Simvastatin induced a reduction of tumor cell growth. In both cell lines, simvastatin induced apoptosis and impaired cell cycle progression as depicted by the greater rates of G0/G1-phase cells than the rates of S-phase cells. Protein expression levels of cell cycle regulating proteins CDK1, CDK2, CDK4, cyclin D1, cyclin E, p19 and p27 were markedly altered by simvastatin. Moreover, CDC2, CCND1 and CDCN2D mRNA expressions were also altered by drug treatment. Collectively, these results suggest that simvastatin induces apoptosis in tumor cells and its anti-proliferative activity was accompanied by inhibition of cyclin-dependent kinases and cyclins, whereas CDK inhibitors p19 and p27 were enhanced. These results may provide novel insights into simvastatin tumor-suppressive action.
Borna Relja; Frank Meder; Kerstin Wilhelm; Dirk Henrich; Ingo Marzi; Mark Lehnert
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  International journal of molecular medicine     Volume:  26     ISSN:  1791-244X     ISO Abbreviation:  Int. J. Mol. Med.     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-09-29     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9810955     Medline TA:  Int J Mol Med     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  735-41     Citation Subset:  IM    
Department of Trauma Surgery, Johann Wolfgang Goethe University, Frankfurt am Main, Germany.
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