Lovastatin-induced RhoA modulation and its effect on senescence in prostate cancer cells

• DOI: 10.1016/j.bbrc.2005.11.075
• Publication Date: 2005-11-29T12:41:32Z
• Authors: Jeeyun Lee; Inkyoung Lee; Chaehwa Park; Won Ki Kang
• Keywords: Male; Dose-Response Relationship, Drug; Cell Cycle; Prostatic Neoplasms; Antineoplastic Agents; 3. Good health; Gene Expression Regulation, Neoplastic; 03 medical and health sciences; 0302 clinical medicine; Cell Line, Tumor; Humans; Lovastatin; rhoA GTP-Binding Protein; Cellular Senescence

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.