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Indomethacin sensitizes TRAIL-resistant melanoma cells to TRAIL-induced apoptosis through ROS-MEDIATED UPREGULATION OF DEATH RECEPTOR 5 AND DOWNREGULATION OF SURVIVIN
Tse A.K.-W.; Cao H.-H.; Cheng C.-Y.; Kwan H.-Y.; Yu H.; Fong W.-F.; Yu Z.-L.
2014
Source PublicationJournal of Investigative Dermatology
ISSN15231747 0022202X
Volume134Issue:5Pages:1397-1407
Abstract

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has attracted considerable attention owing to its selective killing of tumor cells but not normal cells. Melanoma shows weak response to TRAIL because of its low level of TRAIL death receptors. Here, we investigated whether indomethacin, a nonsteroidal anti-inflammatory drug, can potentiate TRAIL-induced apoptosis in melanoma cells. We showed that indomethacin was capable of promoting TRAIL-induced cell death and apoptosis in A375 melanoma cells. Mechanistically, indomethacin induced cell surface expression of death receptor 5 (DR5) in melanoma cells and also in various types of cancer cells. DR5 knockdown abolished the enhancing effect of indomethacin on TRAIL responses. Induction of the DR5 by indomethacin was found to be p53 independent but dependent on the induction of CCAAT/enhancer-binding protein homologous protein (CHOP). Knockdown of CHOP abolished indomethacin-induced DR5 expression and the associated potentiation of TRAIL-mediated cell death. In addition, indomethacin-induced reactive oxygen species (ROS) production preceded upregulation of CHOP and DR5, and consequent sensitization of cells to TRAIL. We also found that indomethacin treatment downregulated survivin via ROS and the NF-κB-mediated signaling pathways. Interestingly, indomethacin also converted TRAIL-resistant melanoma MeWo and SK-MEL-5 cells into TRAIL-sensitive cells. Taken together, our results indicate that indomethacin can potentiate TRAIL-induced apoptosis through upregulation of death receptors and downregulation of survivin.

DOI10.1038/jid.2013.471
URLView the original
Indexed BySCI
Language英语
WOS Research AreaDermatology
WOS SubjectDermatology
WOS IDWOS:000334570300031
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Cited Times [WOS]:31   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
AffiliationHong Kong Baptist University
Recommended Citation
GB/T 7714
Tse A.K.-W.,Cao H.-H.,Cheng C.-Y.,et al. Indomethacin sensitizes TRAIL-resistant melanoma cells to TRAIL-induced apoptosis through ROS-MEDIATED UPREGULATION OF DEATH RECEPTOR 5 AND DOWNREGULATION OF SURVIVIN[J]. Journal of Investigative Dermatology,2014,134(5):1397-1407.
APA Tse A.K.-W..,Cao H.-H..,Cheng C.-Y..,Kwan H.-Y..,Yu H..,...&Yu Z.-L..(2014).Indomethacin sensitizes TRAIL-resistant melanoma cells to TRAIL-induced apoptosis through ROS-MEDIATED UPREGULATION OF DEATH RECEPTOR 5 AND DOWNREGULATION OF SURVIVIN.Journal of Investigative Dermatology,134(5),1397-1407.
MLA Tse A.K.-W.,et al."Indomethacin sensitizes TRAIL-resistant melanoma cells to TRAIL-induced apoptosis through ROS-MEDIATED UPREGULATION OF DEATH RECEPTOR 5 AND DOWNREGULATION OF SURVIVIN".Journal of Investigative Dermatology 134.5(2014):1397-1407.
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