- Title
- TRAIL-induced apoptosis of human melanoma cells involves activation of caspase-4
- Creator
- Mao, Zhi Gang; Jiang, Chen Chen; Thorne, Rick F.; Zhang, Xu Dong; Yang, Fan
- Relation
- Apoptosis Vol. 15, Issue 10, p. 1211-1222
- Publisher Link
- http://dx.doi.org/10.1007/s10495-010-0513-9
- Publisher
- Springer
- Resource Type
- journal article
- Date
- 2010
- 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.
- Subject
- TRAIL; caspase-4; melanoma; apoptosis
- Identifier
- uon:9621
- Identifier
- http://hdl.handle.net/1959.13/922695
- Identifier
- ISSN:1360-8185
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