Document Detail


Disulfiram/copper complex activated JNK/c-jun pathway and sensitized cytotoxicity of doxorubicin in doxorubicin resistant leukemia HL60 cells.
MedLine Citation:
PMID:  21911303     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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.
Authors:
Bing Xu; Pengcheng Shi; Ivo S Fombon; Yanyan Zhang; Fen Huang; Weiguang Wang; Shuyun Zhou
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-9-10
Journal Detail:
Title:  Blood cells, molecules & diseases     Volume:  -     ISSN:  1096-0961     ISO Abbreviation:  -     Publication Date:  2011 Sep 
Date Detail:
Created Date:  2011-9-13     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9509932     Medline TA:  Blood Cells Mol Dis     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011 Elsevier Inc. All rights reserved.
Affiliation:
Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, PR China.
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