title: TRAIL and triptolide: an effective combination that induces apoptosis in pancreatic cancer cells.
abstract: BACKGROUND
  An emerging therapy in oncology is the induction of apoptotic cell death through anti-death receptor therapy. However, pancreatic cancer is resistant to apoptosis including anti-death receptor therapy. We have previously described how triptolide decreases resistance to apoptosis in pancreatic cancer cells in vitro and in vivo. We hypothesized that triptolide decreases tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) resistance in pancreatic cancer cells. The aim of this study was to evaluate the effects that combined therapy with TRAIL and triptolide have on different parameters of apoptosis.
  
  
  METHODS
  Four different pancreatic cancer cell lines were exposed to triptolide, TRAIL, or a combination of both drugs. We assessed the effects that combined therapy with TRAIL and triptolide has on cell viability, apoptosis, caspase-3 and caspase-9 activities, and poly(ADP)-ribose polymerase cleavage.
  
  
  RESULTS
  Pancreatic cancer cells were resistant to TRAIL therapy; however, combined therapy with triptolide and TRAIL significantly decreased the cell viability in all the cell lines and increased apoptotic cell death as a result of caspase-3 and caspase-9 activation.
  
  
  CONCLUSIONS
  Pancreatic cancer is highly resistant to anti-death receptor therapy, but combined therapy with TRAIL and triptolide is an effective therapy that induces apoptotic cell death in pancreatic cancer cells.
authors.affiliation: Department of Surgery, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Borja-Cacho
authors.forename: Yumi
authors.initials: Y
authors.lastname: Yokoyama
authors.forename: Rohit K
authors.initials: RK
authors.lastname: Chugh
authors.forename: Nameeta R
authors.initials: NR
authors.lastname: Mujumdar
authors.forename: Vikas
authors.initials: V
authors.lastname: Dudeja
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Clawson
authors.forename: Rajinder K
authors.initials: RK
authors.lastname: Dawra
authors.forename: Ashok K
authors.initials: AK
authors.lastname: Saluja
authors.forename: Selwyn M
authors.initials: SM
authors.lastname: Vickers
mesh_terms: D000230:Adenocarcinoma; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004224:Diterpenes / Q000494:pharmacology*; D004852:Epoxy Compounds / Q000494:pharmacology; D006801:Humans; D010190:Pancreatic Neoplasms; D010616:Phenanthrenes / Q000494:pharmacology*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000494:pharmacology*
chemical_list: D018906:Antineoplastic Agents, Alkylating; D004224:Diterpenes; D004852:Epoxy Compounds; D010616:Phenanthrenes; D053221:TNF-Related Apoptosis-Inducing Ligand; C001899:triptolide