Signaling and function of caspase and c-Jun N-terminal kinase in cisplatin-induced apoptosis

Myoung Sook Koo, Young Guen Kwon, Joon Hong Park, Won Jin Choi, Timothy R. Billiar, Young Myeong Kim

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Caspases and c-Jun N-terminal kinase (JNK) are activated in tumor cells during induction of apoptosis. We investigated the signaling cascade and function of these enzymes in cisplatin-induced apoptosis. Treatment of Jurkat T-cells with cisplatin induced cell death with DNA fragmentation and activation of caspase and JNK. Bcl-2 overexpression suppressed activation of both enzymes, whereas p35 and CrmA inhibited only the DEVDase (caspase-3-like) activity, indicating that the activation of these enzymes may be differentially regulated. Cisplatin induced apoptosis with the cytochrome c release and caspase-3 activation in both wild-type and caspase-8-deficient JB-6 cells, while the Fas antibody induced these apoptotic events only in wild-type cells. This indicates that caspase-8 activation is required for Fas-mediated apoptosis, but not cisplatin-induced cell death. On the other hand, cisplatin induced the JNK activation in both the wild-type and JB-6 cells, and the caspase-3 inhibitor Z-DEVD-fmk did not inhibit this activation. The JNK overexpression resulted in a higher JNK activity, AP-1 DNA binding activity, and metallothionein expression than the empty vector-transfected cells following cisplatin treatment. It also partially protected the cells from cisplatin-induced apoptosis by decreasing DEVDase activity. These data suggest that the cisplatin-induced apoptotic signal is initiated by the caspase-8-independent cytochrome c release, and the JNK activation protects cells from cisplatin-induced apoptosis via the metallothionein expression.

Original languageEnglish
Pages (from-to)194-201
Number of pages8
JournalMolecules and cells
Volume13
Issue number2
Publication statusPublished - 2002 Apr 1

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Signaling and function of caspase and c-Jun N-terminal kinase in cisplatin-induced apoptosis'. Together they form a unique fingerprint.

  • Cite this

    Koo, M. S., Kwon, Y. G., Park, J. H., Choi, W. J., Billiar, T. R., & Kim, Y. M. (2002). Signaling and function of caspase and c-Jun N-terminal kinase in cisplatin-induced apoptosis. Molecules and cells, 13(2), 194-201.