Disulfiram/copper complex activated JNK/c-jun pathway and sensitized cytotoxicity of doxorubicin in doxorubicin resistant leukemia HL60 cells
- PMID: 21911303
- DOI: 10.1016/j.bcmd.2011.08.004
Disulfiram/copper complex activated JNK/c-jun pathway and sensitized cytotoxicity of doxorubicin in doxorubicin resistant leukemia HL60 cells
Abstract
Resistance to chemotherapy and non-specific cytotoxicity are the major challenges to the treatment of acute myeloid leukemia (AML). In this study, we demonstrated that the disulfiram/copper (DS/Cu) complex alone exhibited cytotoxicity to doxorubicin (Dox) resistant leukemia HL60 cells (HL60/Dox) and enhanced cytotoxicity of Dox to HL60/Dox cells. DS/Cu inhibited Bcl-2 expression and enhanced Dox-induced apoptosis. DS/Cu/Dox in combination significantly induced c-Jun expression and JNK and c-Jun phosphorylation. JNK inhibitor Sp600125 attenuated DS/Cu/Dox-induced apoptosis and suppressed DS/Cu/Dox-induced protein expression in JNK/c-jun pathway. This study suggested that DS/Cu complex may re-sensitize HL60/Dox cells to Dox through activating JNK/c-jun as well as inhibiting anti-apoptotic bcl-2 expression.
Copyright © 2011 Elsevier Inc. All rights reserved.
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