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Apicidin potentiates the imatinib-induced apoptosis of Bcr–Abl-positive human leukaemia cells by enhancing the activation of mitochondria-dependent caspase cascades

Authors
 Seung Tae Lee  ;  Jin Seok Kim  ;  Yoo Hong Min  ;  Yun Woong Ko  ;  Jee Sook Hahn  ;  Hoyoung Maeng  ;  June-Won Cheong  ;  Hoi Kyung Jeung 
Citation
 British Journal of Haematology, Vol.124(2) : 166-178, 2004 
Journal Title
 British Journal of Haematology 
ISSN
 0007-1048 
Issue Date
2004
Abstract
Apicidin, a histone deacetylase inhibitor, is a novel cyclic tetrapeptide with potent antiproliferative activity against various cancer cells. We examined whether apicidin potentiates the imatinib-induced apoptosis of Bcr–Abl-positive human leukaemia cells. In K562 cells, the co-administration of minimally toxic concentrations of imatinib and apicidin (imatinib/apicidin) for 48 h produced a marked increase in mitochondrial damage, processing of caspase cascades and apoptosis. Similar results were observed in leukaemic blasts obtained from patients with chronic myeloid leukaemia in blast crisis. Imatinib/apicidin co-treatment for 48 h resulted in a near complete loss of the full-length XIAP (X-linked inhibitor of apoptosis) protein, with a corresponding increase in the 29-kDa XIAP cleavage product. Both the degradation of XIAP and increased release of second mitochondria-derived activator of caspase/direct IAP-binding protein with low pI (Smac/DIABLO) into the cytosol were abrogated by pretreatment with the caspase-3 inhibitor DEVD-CHO. Imatinib/apicidin co-treatment for 48 h produced a prominent decrease in Bcr–Abl protein levels in a caspase-dependent manner. In summary, these data indicate that apicidin potentiates the imatinib-induced apoptosis of Bcr–Abl-positive leukaemia cells through the enhanced activation of the mitochondria-dependent caspase cascades, accompanied by caspase-dependent downregulation of Bcr–Abl and XIAP. These findings generate a rationale for further investigation of apicidin and imatinib as a potential therapeutic strategy in Bcr–Abl-positive leukaemias.
Full Text
http://onlinelibrary.wiley.com/doi/10.1046/j.1365-2141.2003.04759.x/abstract
DOI
10.1046/j.1365-2141.2003.04759.x
Appears in Collections:
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원)
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실)
Yonsei Authors
고윤웅(Ko, Yun Woong)
김진석(Kim, Jin Seok) ORCID logo https://orcid.org/0000-0001-8986-8436
맹호영(Maeng, Ho Young)
민유홍(Min, Yoo Hong) ORCID logo https://orcid.org/0000-0001-8542-9583
이승태(Lee, Seung Tae)
정준원(Cheong, June-Won) ORCID logo https://orcid.org/0000-0002-1744-0921
정회경(Jeung, Hoi Kyung)
한지숙(Hahn, Jee Sook)
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URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/111336
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