title: Tunicamycin sensitizes human prostate cells to TRAIL-induced apoptosis             by upregulation of TRAIL receptors and downregulation of cIAP2.
abstract: The addition of tunicamycin to prostate cancer cells enhances cell death mediated by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). In this study, we investigated whether tunicamycin, an endoplasmic reticulum stress inducer, can potentiate TRAIL-induced apoptosis in human prostate cancer cells. We evaluated the combination of tunicamycin and TRAIL and found synergistic promotion of apoptosis in prostate cancer cells. The combined treatment with tunicamycin and TRAIL significantly induced apoptosis, and stimulated caspase-3, -8 and -9 activity, as well as the cleavage of poly (ADP-ribose) polymerase. We found that tunicamycin promoted TRAIL-induced apoptosis by the upregulation of death receptor (DR)4 and DR5 and the downregulation of cellular inhibitor of apoptosis 2 (cIAP2). In addition, downregulation of cIAP2 expression using small interfering RNA significantly attenuated the apoptosis induced by TRAIL. Taken together, our results demonstrate that the combination of tunicamycin and TRAIL may provide a novel strategy for treating prostate cancer by overcoming critical mechanisms of apoptosis resistance.
authors.affiliation: Department of Molecular Biology and Immunology, Kosin University                     College of Medicine, Busan 602-703, Republic of Korea.
authors.forename: Young-Hwa
authors.initials: YH
authors.lastname: Jung
authors.forename: Eun Jin
authors.initials: EJ
authors.lastname: Lim
authors.forename: Jeonghoon
authors.initials: J
authors.lastname: Heo
authors.forename: Taeg Kyu
authors.initials: TK
authors.lastname: Kwon
authors.forename: Young-Ho
authors.initials: YH
authors.lastname: Kim
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D000075747:Baculoviral IAP Repeat-Containing 3 Protein; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor / Q000187:drug effects; D002470:Cell Survival; D015536:Down-Regulation; D004357:Drug Synergism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics* / Q000378:metabolism; D008297:Male; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics* / Q000378:metabolism; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000494:pharmacology*; D014415:Tunicamycin / Q000494:pharmacology*; D044767:Ubiquitin-Protein Ligases; D015854:Up-Regulation
chemical_list: D000970:Antineoplastic Agents; D051034:Inhibitor of Apoptosis Proteins; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014415:Tunicamycin; C494832:BIRC3 protein, human; D000075747:Baculoviral IAP Repeat-Containing 3 Protein; D044767:Ubiquitin-Protein Ligases; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D020169:Caspases