The mechanism of STI571 inducing apoptosis of K562 cells.
OBJECTIVE
To investigate the mechanism of STI571 inducing apoptosis of K562 cells which express P210(BCR/ABL).


METHODS
Apoptosis was analyzed by Annexin-V/PI, DioC6 [3] staining, DCFH-DA staining, DNA-PI staining and DNA ladder. Western blot was used to analyse mitochondrial and cytosolic cyto C, Bcl-X(L), caspase-3, actin protein and the level of tyrosine phosphorylation.


RESULTS
After exposure to STI571, K562 cells were induced to apoptosis. Tyrosine phosphorylation level of P210(BCR/ABL) and Bcl-X(L) was decreased. Caspase-3 was activated and there was an cytosolic accumulation of cyto C.


CONCLUSIONS
STI571 could rapidly decrease the tyrosine phosphorylation level of P210(BCR/ABL). The signal pathway mediated by the cytosolic translocation of mitochondrial cyto C was one of the mechanisms that STI571 inducing apoptosis. STI571 was an effective gene targeting therapeutic agent.
Qin
Yazhen
Y
Institute of Hematology, People's Hospital, Peking University, Beijing 100044, China.
Chen
Shanshan
S
Chang
Yan
Y
Fu
Jiayu
J
Wang
Xinjuan
X
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D001549:Benzamides; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D003574:Cytochrome c Group / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004792:Enzyme Precursors / Q000378:metabolism; D016044:Fusion Proteins, bcr-abl / Q000378:metabolism; D006801:Humans; D000068877:Imatinib Mesylate; D020014:K562 Cells; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism
D000970:Antineoplastic Agents; D001549:Benzamides; D003574:Cytochrome c Group; D004792:Enzyme Precursors; D010879:Piperazines; D011743:Pyrimidines; D017382:Reactive Oxygen Species; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases