Document Detail


Lovastatin-induced RhoA modulation and its effect on senescence in prostate cancer cells.
MedLine Citation:
PMID:  16316623     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Lovastatin inhibits a 3-hydroxy 3-methylglutaryl coenzyme A reductase and prevents the synthesis of cholesterol precursors, such as farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate (GGPP), responsible for important cell signaling in cell proliferation and migration. Recently, the anti-cancer effect of lovastatin has been suggested in various tumor types. In this study, we showed that a low dose lovastatin induced senescence and G1 cell cycle arrest in human prostate cancer cells. Addition of GGPP or mevalonate, but not FPP, prevented the lovastatin-induced G1 phase cell cycle arrest and cell senescence. We found that constitutively active RhoA (caRhoA) reversed lovastatin-induced senescence in caRhoA-transfected PC-3 cells. Thus, we postulate that modulation of RhoA may be critical in lovastatin-induced senescence in PC-3 cells.
Authors:
Jeeyun Lee; Inkyoung Lee; Chaehwa Park; Won Ki Kang
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Biochemical and biophysical research communications     Volume:  339     ISSN:  0006-291X     ISO Abbreviation:  Biochem. Biophys. Res. Commun.     Publication Date:  2006 Jan 
Date Detail:
Created Date:  2005-12-13     Completed Date:  2006-02-23     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0372516     Medline TA:  Biochem Biophys Res Commun     Country:  United States    
Other Details:
Languages:  eng     Pagination:  748-54     Citation Subset:  IM    
Affiliation:
Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
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MeSH Terms
Descriptor/Qualifier:
Antineoplastic Agents / administration & dosage
Cell Aging / drug effects*
Cell Cycle / drug effects*
Cell Line, Tumor
Dose-Response Relationship, Drug
Gene Expression Regulation, Neoplastic / drug effects
Humans
Lovastatin / administration & dosage*
Male
Prostatic Neoplasms / metabolism*,  pathology*
rhoA GTP-Binding Protein / metabolism*
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 75330-75-5/Lovastatin; EC 3.6.5.2/rhoA GTP-Binding Protein

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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