Please use this identifier to cite or link to this item: http://hdl.handle.net/1959.13/922695

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Title
TRAIL-induced apoptosis of human melanoma cells involves activation of caspase-4
Author/Creator
Mao, Zhi Gang;  Jiang, Chen Chen;  Thorne, Rick F.;  Zhang, Xu Dong;  Yang, Fan
Institution
The University of Newcastle. Faculty of Health, School of Medicine and Public Health
Description
Although it is conventionally regarded as an inflammatory caspase, recent studies have shown that caspase-4 plays a role in induction of apoptosis by endoplasmic reticulum (ER) stress. We report here that activation of caspase-4 is also involved in induction of apoptosis by TNF-related apoptosis-inducing ligand (TRAIL) in human melanoma cells. Treatment with TRAIL resulted in activation of caspase-4. This appeared to be mediated by caspase-3, in that caspase-4 was activated later than caspase-8, -9, and -3, and that inhibition of caspase-3 blocked TRAIL-induced caspase-4 activation. Notably, TRAIL triggered ER stress in melanoma cells as shown by up-regulation of the GRP78 protein and the spliced form of XBP-1 mRNA. This seemed to be necessary for activation of caspase-4, as activation of caspase-3 by agents that did not trigger ER stress did not cause activation of caspase-4. Importantly, inhibition of caspase-4 also partially blocked caspase-3 activation, suggesting that activation of caspase-4 may be positive feed-back mechanism to further enhance caspase-3 activation. Collectively, these results show that activation of caspase-4 contributes to TRAIL-induced apoptosis and is associated with induction of ER stress by TRAIL in melanoma cells, and may have important implications for improving therapeutic efficacies of TRAIL in melanoma.
Relation
Apoptosis Vol. 15, Issue 10, p. 1211-1222
Publisher Link
http://dx.doi.org/10.1007/s10495-010-0513-9
Date
2010
Publisher
Springer
Keyword(s)
TRAIL;  caspase-4;  melanoma;  apoptosis
Resource Type
journal article
Identifier
http://hdl.handle.net/1959.13/922695
Identifier
ISSN:1360-8185
Reviewed
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Subject
"Apoptosis"
 
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