Mechanism of simvastatin-induced K562 cell apoptosis.
Statins are being widely used for the therapy and prevention of several types of tumors, including human chronic myelogenous leukemia, but the underlying molecular mechanisms still remain unknown. Therefore, inhibition of cell proliferation, apoptosis and involved molecules were investigated in K562 cells after incubation with simvastatin.The results showed that simvastatin diminished K562 cell proliferation and induced apoptosis. At the same time, the level of reactive oxygen species (ROS) and intracellular calcium concentration increased. Furthermore, nitric oxide (NO) content and inducible NO synthase (iNOS) mRNA expression were significantly higher in the simvastatin-treated group than in the corresponding control group. The elevated ROS level and intracellular calcium concentration, enhanced mRNA expression of iNOS and total NO content might be responsible for the apoptotic and anti-proliferative effects of simvastatin in K562 cells.
Yang
Yong-Chang
YC
Clinical Laboratory Department, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, China.
Xiao
Dai-Wen
DW
Liu
Hua
H
Chuan
Liang-Min
LM
Zeng
Ya-Li
YL
Zhou
Ding-An
DA
Liu
Wen
W
Xu
Guo-Qiang
GQ
Huang
Wen-Fang
WF
D017209:Apoptosis / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D020014:K562 Cells; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D019821:Simvastatin / Q000494:pharmacology*
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D019821:Simvastatin; D052247:Nitric Oxide Synthase Type II; D002118:Calcium