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 language | English (US) |
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Pages (from-to) | 156-166 |
Number of pages | 11 |
Journal | Cancer Letters |
Volume | 348 |
Issue number | 1-2 |
DOIs | |
State | Published - 2014 |
Keywords
- Apoptosis
- Death receptor
- LMP
- MOMP
- Pancreatic cancer
- TRAIL
- Triptolide