TRAIL and triptolide: an effective combination that induces apoptosis in pancreatic cancer cells.
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.
Borja-Cacho
Daniel
D
Department of Surgery, University of Minnesota, Minneapolis, MN 55455, USA.
Yokoyama
Yumi
Y
Chugh
Rohit K
RK
Mujumdar
Nameeta R
NR
Dudeja
Vikas
V
Clawson
Kimberly A
KA
Dawra
Rajinder K
RK
Saluja
Ashok K
AK
Vickers
Selwyn M
SM
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*
D018906:Antineoplastic Agents, Alkylating; D004224:Diterpenes; D004852:Epoxy Compounds; D010616:Phenanthrenes; D053221:TNF-Related Apoptosis-Inducing Ligand; C001899:triptolide