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Cardiotoxin III induces c‐jun N‐terminal kinase‐dependent apoptosis in HL‐60 human leukaemia cells
Author(s) -
Chien ChingMing,
Yang ShengHuei,
Yang ChunChieh,
Chang LongSen,
Lin ShinneRen
Publication year - 2008
Publication title -
cell biochemistry and function
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.933
H-Index - 61
eISSN - 1099-0844
pISSN - 0263-6484
DOI - 10.1002/cbf.1420
Subject(s) - apoptosis , kinase , cardiotoxin , terminal (telecommunication) , chemistry , microbiology and biotechnology , c jun , cancer research , biology , biochemistry , gene , venom , computer science , transcription factor , telecommunications
Cardiotoxin III (CTX III), a basic polypeptide with 60 amino acid residues isolated from Naja naja atra venom, has been reported to have anticancer activity. The molecular effects of CTX III on HL‐60 cells were dissected in the present study. We found that the antiproliferative action of CTX III on HL‐60 cells was mediated through apoptosis, as characterized by an increase of sub G 1 population, DNA fragmentation and poly(ADP‐ribose) polymerase (PARP) cleavage. Upregulation of Bax, downregulation of Bcl‐2, the release of mitochondrial cytochrome c to cytosol and the activations of capase‐9 and ‐3 were noted, while CTX III had no appreciable effect on the levels of Bcl‐X L and Bad proteins. Moreover, c‐Jun N‐terminal kinase (JNK) was activated shortly after CTX III treatment in HL‐60 cells. Consistently, the SP600125 compound, an anthrapyrazolone inhibitor of JNK, suppressed apoptosis induced by CTX III. As expected, this JNK inhibitor also attenuated the modulation of Bax and Bcl‐2, as well as the cytosolic appearance of cytochrome c and the activation of caspase‐3 and caspase‐9 that induced by CTX III. These findings suggest that CTX III can induce apoptosis in HL‐60 cells via the mitochondrial caspase cascade and the activation of JNK is critical for the initiation of the apoptotic death of HL‐60 cells. Copyright © 2007 John Wiley & Sons, Ltd.