title: Triptolide sensitizes pancreatic cancer cells to TRAIL-induced activation of the death receptor pathway.
abstract: The tumor necrosis factor related apoptosis-inducing ligand (TRAIL) causes cancer cell death, but many cancers, including pancreatic cancer, are resistant to TRAIL therapy. A combination of TRAIL and the diterpene triepoxide, triptolide, is effective in inducing pancreatic cancer cell death. Triptolide increases levels of death receptor DR5 and decreases the pro-survival FLICE-like inhibitory protein (c-FLIP), which contribute to the activation of caspase-8. This combination further causes both lysosomal and mitochondrial membrane permeabilization, resulting in cell death. Our study provides a mechanism by which triptolide sensitizes TRAIL resistant cells, which may become a novel therapeutic strategy against pancreatic cancer.
authors.affiliation: Department of Surgery, University of Minnesota, Minneapolis, MN 55455, United States; Department of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing, China. Electronic address: chenz@umn.edu.
authors.forename: Zhiyu
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Surgery, University of Minnesota, Minneapolis, MN 55455, United States. Electronic address: sang0001@umn.edu.
authors.forename: Veena
authors.initials: V
authors.lastname: Sangwan
authors.affiliation: Department of Surgery, University of Minnesota, Minneapolis, MN 55455, United States. Electronic address: sbanerje@umn.edu.
authors.forename: Sulagna
authors.initials: S
authors.lastname: Banerjee
authors.affiliation: Department of Surgery, University of Minnesota, Minneapolis, MN 55455, United States. Electronic address: chugh012@umn.edu.
authors.forename: Rohit
authors.initials: R
authors.lastname: Chugh
authors.affiliation: Department of Surgery, University of Minnesota, Minneapolis, MN 55455, United States. Electronic address: dudej001@umn.edu.
authors.forename: Vikas
authors.initials: V
authors.lastname: Dudeja
authors.affiliation: Department of Surgery, University of Minnesota, Minneapolis, MN 55455, United States. Electronic address: Vickers@umn.edu.
authors.forename: Selwyn M
authors.initials: SM
authors.lastname: Vickers
authors.affiliation: Department of Surgery, University of Minnesota, Minneapolis, MN 55455, United States. Electronic address: asaluja@umn.edu.
authors.forename: Ashok K
authors.initials: AK
authors.lastname: Saluja
mesh_terms: D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D051023:BH3 Interacting Domain Death Agonist Protein / Q000378:metabolism; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein / Q000235:genetics / Q000378:metabolism; D053181:Caspase 8 / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004224:Diterpenes / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D004789:Enzyme Activation; D004852:Epoxy Compounds / Q000494:pharmacology; D006801:Humans; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D051336:Mitochondrial Membranes / Q000187:drug effects / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D010539:Permeability; D010616:Phenanthrenes / Q000494:pharmacology; D034622:RNA Interference; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000494:pharmacology; D014162:Transfection; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D018906:Antineoplastic Agents, Alkylating; C494826:BAX protein, human; D051023:BH3 Interacting Domain Death Agonist Protein; C494814:BID protein, human; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; C506386:CFLAR protein, human; D004224:Diterpenes; D004852:Epoxy Compounds; D010616:Phenanthrenes; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D053221:TNF-Related Apoptosis-Inducing Ligand; C505639:TNFRSF10B protein, human; D051028:bcl-2-Associated X Protein; C001899:triptolide; C505530:CASP8 protein, human; D053181:Caspase 8
keywords: Apoptosis; Death receptor; Pancreatic cancer; TRAIL; Triptolide