title: Simvastatin induces caspase-dependent apoptosis and activates P53 in OCM-1 cells.
abstract: Simvastatin is a cholesterol-lowering drug which exhibits numerous pleiotropic effects including anti-cancer activity. Yet, the anti-cancer effects in choroidal melanoma remain poorly characterized. Therefore, in this study, we investigated the effects of simvastatin on OCM-1 cells growth, apoptosis and cycle. Simvastatin showed an inhibitory effects on OCM-1 cells viability in dose-dependent (2-10 μM) and time-dependent (24-72 h) manner. Further study suggested that simvastatin-induced inhibition OCM-1 cells proliferation was associated with G1 phase arrest, decreased protein and mRNA expression of proliferation marker cyclin D1, cyclin E, cyclin dependent kinase (CDK)2 and increased expression of CDK inhibitory protein P21. In addition, simvastatin resulted in an increase in levels of reactive oxygen species (ROS) in OCM-1 cells and simvastatin significantly triggered apoptosis in OCM-1 cells, which was characterized by increased chromatin condensation, activation of caspase-9 and cleaved-caspase-3, increased expression mitochondrion-related apoptosis protein of P53, Bax and decreased expression of Bcl2 and iASPP. Collectively, our study demonstrated that simvastatin can efficiently inhibit proliferation and induce apoptosis in OCM-1 cells.
authors.affiliation: Department of Ophthalmology, Second Hospital of JiLin University, ChangChun 130041, China. wangying9201@163.com
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Shao-Lin
authors.initials: SL
authors.lastname: Xu
authors.forename: Ya-Zhen
authors.initials: YZ
authors.lastname: Wu
authors.forename: Mei-Sheng
authors.initials: MS
authors.lastname: Zhao
authors.forename: Wen-Jing
authors.initials: WJ
authors.lastname: Xu
authors.forename: Hai-Yan
authors.initials: HY
authors.lastname: Yang
authors.forename: Yu-Xin
authors.initials: YX
authors.lastname: Li
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D020169:Caspases / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002830:Choroid Neoplasms / Q000201:enzymology / Q000473:pathology*; D019927:Cyclin E / Q000378:metabolism / Q000494:pharmacology; D051357:Cyclin-Dependent Kinase 2 / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D016193:G1 Phase / Q000187:drug effects; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D008545:Melanoma / Q000201:enzymology / Q000473:pathology*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D015513:Oncogene Proteins; D017382:Reactive Oxygen Species / Q000378:metabolism; D019821:Simvastatin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; C475820:CCNE1 protein, human; D019927:Cyclin E; D050759:Cyclin-Dependent Kinase Inhibitor p21; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D015513:Oncogene Proteins; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D019821:Simvastatin; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases
keywords: OCM-1 cells; apoptosis; caspase-dependent pathway; cell cycle arrest; simvastatin