期刊
CHEMICO-BIOLOGICAL INTERACTIONS
卷 193, 期 2, 页码 162-171出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.cbi.2011.06.007
关键词
Arsenic trioxide; Apoptosis; Irradiation; HL-60
资金
- National Science Council, Taiwan [NSC 98-2314-B-006-034-MY2]
- Sinlau Christian Hospital, Tainan, Taiwan
The induction of apoptotic cell death is a significant mechanism of tumor cells under the influence of radio-/chemotherapy, and resistance to these treatments has been linked to some cancer cell lines with a low propensity for apoptosis. The present study aimed to investigate the enhanced effects and mechanisms in apoptosis and the cycle distribution of HL-60 cells, a human leukemia cell line lacking a functional p53 protein, after combination treatment with arsenic trioxide (ATO) and irradiation (IR). Our results indicated that combined treatment led to increased cytotoxicity and apoptotic cell death in HL-60 cells, which was correlated with the activation of cdc-2 and increased expression of cyclin B. the induction of intracellular reactive oxygen species (ROS) generation, the loss of mitochondria membrane potential, and the activation of caspase-3. The combined treatment of HL-60 cells pre-treated with Z-VAD or NAC resulted in a significant reduction in apoptotic cells. In addition, activation of JNK and p38 MAPK may be involved in combined treatment-mediated apoptosis. The data suggest that a combination of IR and ATO could be a potential therapeutic strategy against p53-deficient leukemia cells. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
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