Gleevec induces apoptosis in K562 cells through activating caspase-3.
- Author:
Qiao-Hong PU
;
Qing-Qing WU
;
Xiao-Bao JIN
;
Wei-Zhang WANG
- Publication Type:Journal Article
- MeSH:
Amino Acid Chloromethyl Ketones;
Apoptosis;
drug effects;
Benzamides;
pharmacology;
Caspase 3;
metabolism;
Cell Cycle;
drug effects;
Humans;
Imatinib Mesylate;
K562 Cells;
Phosphorylation;
Piperazines;
pharmacology;
Pyrimidines;
pharmacology
- From:
Acta Pharmaceutica Sinica
2014;49(8):1124-1129
- CountryChina
- Language:Chinese
-
Abstract:
The present study is to elucidate the mechanisms underlying Gleevec-induced apoptosis of chronic myeloid leukemia (CML) K562 cells in vitro. The apoptotic cell death and cell cycle distribution after Gleevec treatment and the effect of PDCD4 siRNA on Gleevec-induced apoptosis of K562 cells were analyzed by flow cytometry. The effect of Gleevec on p-Crkl, caspase-3, PARP and PDCD4 protein levels, and the knockdown efficacy of PDCD4 siRNA were detected by Western blotting. The results showed that Gleevec dramatically suppressed the phosphorylation level of Crkl in a dose-dependent manner and induced significant apoptosis and G0/G1 cell cycle arrest of K562 cells in time- and dose-dependent manners. In addition, Gleevec activated caspase-3 and its downstream substrates PARP, and the caspase pan inhibitor Z-VAD-FMK (50 micromol x L(-1)) markedly reduced Gleevec-induced apoptosis from 47.97% +/- 10.56% to 31.05% +/- 9.206% (P < 0.05). Moreover, Gleevec significantly increased the protein expression of programmed cell death 4 (PDCD4). PDCD4 knockdown by siRNA reduced Gleevec-induced apoptosis from 46.97% +/- 14.32% to 42.8% +/- 11.43%. In summary, Gleevec induced apoptosis in K562 cells via caspase-3 activation.
