Triptolide sensitizes pancreatic cancer cells to TRAIL-induced activation of the Death Receptor pathway

Zhiyu Chen, Veena Sangwan, Sulagna Banerjee, Rohit Chugh, Vikas Dudeja, Selwyn M. Vickers, Ashok K. Saluja

Research output: Contribution to journalArticle

45 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)156-166
Number of pages11
JournalCancer Letters
Volume348
Issue number1-2
DOIs
StatePublished - 2014

Keywords

  • Apoptosis
  • Death receptor
  • LMP
  • MOMP
  • Pancreatic cancer
  • TRAIL
  • Triptolide

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