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Curcumin sensitizes tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis through CHOP-independent DR5 upregulation.

Authors
Jung, EM; Park, JW; Choi, KS; Lee, HI; Lee, KS; Kwon, TK
Citation
Carcinogenesis, 27(10):2008-2017, 2006
Journal Title
Carcinogenesis
ISSN
0143-33341460-2180
Abstract
Death receptor DR5 (DR5/TRAIL-R2) is an apoptosis-inducing membrane receptor for tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). In this study, we showed that curcumin, a plant product containing the phenolic phytochemical, is a potent enhancer of TRAIL-induced apoptosis through upregulation of DR5 expression. Both treatment with DR5/Fc chimeric protein and silencing of DR5 expression using small interfering RNA (siRNA) attenuated curcumin plus TRAIL-induced apoptosis, showing that the critical role of DR5 in this cell death. Curcumin also induced the expression of a potential pro-apoptotic gene, C/EBP homologous protein (CHOP), both at its mRNA and protein levels. However, suppression of CHOP expression by small interfering RNA did not abrogate the curcumin-mediated induction of DR5 and the cell death induced by curcumin plus TRAIL, demonstrating that CHOP is not involved in curcumin-induced DR5 upregulation. Taken together, the present study demonstrates that curcumin enhances TRAIL-induced apoptosis by CHOP-independent upregulation of DR5.
MeSH terms
Acetylcysteine/pharmacologyApoptosis/drug effects*Apoptosis Regulatory Proteins/pharmacology*Curcumin/pharmacology*Drug SynergismGene Expression Regulation/drug effects*HumansMembrane Glycoproteins/pharmacology*Promoter Regions, GeneticRNA, Messenger/analysisReactive Oxygen SpeciesReceptors, TNF-Related Apoptosis-Inducing LigandReceptors, Tumor Necrosis Factor/genetics*TNF-Related Apoptosis-Inducing LigandTranscription Factor CHOP/physiology*Tumor Necrosis Factor-alpha/pharmacology*Up-Regulation
DOI
10.1093/carcin/bgl026
PMID
16613838
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Journal Papers > School of Medicine / Graduate School of Medicine > Biochemistry & Molecular Biology
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