Journal
CANCER LETTERS
Volume 348, Issue 1-2, Pages 156-166Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2014.03.016
Keywords
TRAIL; Pancreatic cancer; Triptolide; Apoptosis; Death receptor
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Funding
- Masonic Cancer Center, the Department of Surgery, Pancreatic Cancer SPORE grant to the University of Minnesota and University of Alabama
- Katherine and Robert Goodale Foundation
- Hirshberg Foundation
- National Institute of Health [R01CA124723, R01 CA170496]
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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. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
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