Oligomycin A enhances apoptotic effect of TRAIL through CHOP-mediated death receptor 5 expression

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Title
Oligomycin A enhances apoptotic effect of TRAIL through CHOP-mediated death receptor 5 expression
Author(s)
L He; Jae-Hyuk Jang; H G Choi; S M Lee; M H Nan; Sook-Jung Jeong; Z Dong; Y T Kwon; K S Lee; K W Lee; J K Chung; Jong Seog AhnBo Yeon Kim
Bibliographic Citation
Molecular Carcinogenesis, vol. 52, no. 2, pp. 85-93
Publication Year
2013
Abstract
Development of resistance to TNF-related apoptosis-inducing ligand (TRAIL) in tumor cells is one of the important problems in cancer treatment. Despite the previous report demonstrating that oligomycin suppressed TNF-induced apoptosis, in our screening of small molecules enhancing cancer cell death to TRAIL, oligomycin A (OMA) was found to enhance TRAIL-induced apoptosis in HeLa cells. CCAAT/enhancer-binding protein homologous protein (CHOP) was found to directly bind to death receptor 5 (DR5) promoter through endoplasmic reticulum stress (ER-stress) signaling and sensitize the cells to TRAIL. Among ER-stress associated proteins, OMA triggered the inositol-requiring enzyme 1 (IRE1) signaling pathway, leading to X-binding protein 1 (XBP1) splicing, CHOP expression and DR5 upregulation. In contrast, small-interfering RNA (siRNA) of CHOP reduced the number of apoptotic cells in response to the co-treatment of TRAIL and OMA. Collectively, our data suggest that OMA enhances apoptotic death of cervical cancer cells to TRAIL through upregulation of CHOP-mediated DR5 expression following ER-stress.
Keyword
ChemosensitizationCHOPDR5Oligomycin ATRAIL
ISSN
0899-1987
Publisher
Wiley
DOI
http://dx.doi.org/10.1002/mc.21831
Type
Article
Appears in Collections:
Ochang Branch Institute > Chemical Biology Research Center > 1. Journal Articles
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