Lovastatin-induced RhoA modulation and its effect on senescence in prostate cancer cells.
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.
Lee
Jeeyun
J
Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
Lee
Inkyoung
I
Park
Chaehwa
C
Kang
Won Ki
WK
D000970:Antineoplastic Agents / Q000008:administration & dosage; D002453:Cell Cycle / Q000187:drug effects*; D045744:Cell Line, Tumor; D016922:Cellular Senescence / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008148:Lovastatin / Q000008:administration & dosage*; D008297:Male; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
D000970:Antineoplastic Agents; D008148:Lovastatin; D020742:rhoA GTP-Binding Protein