TRAIL and triptolide

An effective combination that induces apoptosis in pancreatic cancer cells

Daniel Borja-Cacho, Yumi Yokoyama, Rohit K. Chugh, Nameeta R. Mujumdar, Vikas Dudeja, Kimberly A. Clawson, Rajinder Dawra, Ashok Saluja, Selwyn M. Vickers

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Introduction: 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.

Original languageEnglish (US)
Pages (from-to)252-260
Number of pages9
JournalJournal of Gastrointestinal Surgery
Volume14
Issue number2
DOIs
StatePublished - Feb 1 2010
Externally publishedYes

Fingerprint

Pancreatic Neoplasms
Apoptosis
Death Domain Receptors
Therapeutics
Cell Death
Caspase 9
Caspase 3
Cell Survival
triptolide
Cell Line
Ribose
Drug Combinations
Tumor Necrosis Factor-alpha
Ligands

Keywords

  • Apoptosis
  • Death receptor therapy
  • Pancreatic cancer
  • TRAIL
  • Triptolide

ASJC Scopus subject areas

  • Surgery
  • Gastroenterology
  • Medicine(all)

Cite this

Borja-Cacho, D., Yokoyama, Y., Chugh, R. K., Mujumdar, N. R., Dudeja, V., Clawson, K. A., ... Vickers, S. M. (2010). TRAIL and triptolide: An effective combination that induces apoptosis in pancreatic cancer cells. Journal of Gastrointestinal Surgery, 14(2), 252-260. https://doi.org/10.1007/s11605-009-1065-6

TRAIL and triptolide : An effective combination that induces apoptosis in pancreatic cancer cells. / Borja-Cacho, Daniel; Yokoyama, Yumi; Chugh, Rohit K.; Mujumdar, Nameeta R.; Dudeja, Vikas; Clawson, Kimberly A.; Dawra, Rajinder; Saluja, Ashok; Vickers, Selwyn M.

In: Journal of Gastrointestinal Surgery, Vol. 14, No. 2, 01.02.2010, p. 252-260.

Research output: Contribution to journalArticle

Borja-Cacho, Daniel ; Yokoyama, Yumi ; Chugh, Rohit K. ; Mujumdar, Nameeta R. ; Dudeja, Vikas ; Clawson, Kimberly A. ; Dawra, Rajinder ; Saluja, Ashok ; Vickers, Selwyn M. / TRAIL and triptolide : An effective combination that induces apoptosis in pancreatic cancer cells. In: Journal of Gastrointestinal Surgery. 2010 ; Vol. 14, No. 2. pp. 252-260.
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