title: [Gleevec induces apoptosis in K562 cells through activating caspase-3].
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.
authors.forename: Qiao-Hong
authors.initials: QH
authors.lastname: Pu
authors.forename: Qing-Qing
authors.initials: QQ
authors.lastname: Wu
authors.forename: Xiao-Bao
authors.initials: XB
authors.lastname: Jin
authors.forename: Wei-Zhang
authors.initials: WZ
authors.lastname: Wang
mesh_terms: D000590:Amino Acid Chloromethyl Ketones; D017209:Apoptosis / Q000187:drug effects*; D001549:Benzamides / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects; D006801:Humans; D000068877:Imatinib Mesylate; D020014:K562 Cells; D010766:Phosphorylation; D010879:Piperazines / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*
chemical_list: D000590:Amino Acid Chloromethyl Ketones; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D000068877:Imatinib Mesylate; C505407:CASP3 protein, human; D053148:Caspase 3