Oligomycin A enhances apoptotic effect of TRAIL through CHOP-mediated death receptor 5 expression.
Mol Carcinog
; 52(2): 85-93, 2013 Feb.
Article
in En
| MEDLINE
| ID: mdl-23335397
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Oligomycins
/
Apoptosis
/
Transcription Factor CHOP
/
TNF-Related Apoptosis-Inducing Ligand
/
Receptors, TNF-Related Apoptosis-Inducing Ligand
Limits:
Humans
Language:
En
Journal:
Mol Carcinog
Journal subject:
BIOLOGIA MOLECULAR
/
NEOPLASIAS
Year:
2013
Document type:
Article
Affiliation country:
South Korea