Gleevec induces apoptosis in K562 cells through activating caspase-3 / 药学学报
Acta Pharmaceutica Sinica
; (12): 1124-1129, 2014.
Article
en Zh
| WPRIM
| ID: wpr-299158
Biblioteca responsable:
WPRO
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.
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Asunto principal:
Farmacología
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Fosforilación
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Piperazinas
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Pirimidinas
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Benzamidas
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Ciclo Celular
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Apoptosis
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Células K562
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Caspasa 3
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Mesilato de Imatinib
Límite:
Humans
Idioma:
Zh
Revista:
Acta Pharmaceutica Sinica
Año:
2014
Tipo del documento:
Article