Curcumin sensitizes tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis through CHOP-independent DR5 upregulation.
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.
Jung
Eun Mi
EM
Department of Immunology, School of Medicine, Keimyung University, Taegu 700-712, South Korea.
Park
Jong-Wook
JW
Choi
Kyeong Sook
KS
Park
Jeen-Woo
JW
Lee
Hyung Il
HI
Lee
Kyung-Seop
KS
Kwon
Taeg Kyu
TK
D000111:Acetylcysteine / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000494:pharmacology*; D003474:Curcumin / Q000494:pharmacology*; D004357:Drug Synergism; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D008562:Membrane Glycoproteins / Q000494:pharmacology*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000032:analysis; D017382:Reactive Oxygen Species; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics*; D053221:TNF-Related Apoptosis-Inducing Ligand; D051742:Transcription Factor CHOP / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D015854:Up-Regulation
D051017:Apoptosis Regulatory Proteins; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor; D053221:TNF-Related Apoptosis-Inducing Ligand; C505639:TNFRSF10B protein, human; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha; D051742:Transcription Factor CHOP; D003474:Curcumin; D000111:Acetylcysteine