Autophagy in pancreatic cancer: An emerging mechanism of cell death

Nameeta Mujumdar, Ashok K. Saluja

Research output: Contribution to journalShort surveypeer-review

37 Scopus citations

Abstract

Pancreatic cancer, the fourth leading cause of cancer-related death in the United States, is resistant to current chemotherapies. Therefore, identification of different pathways of cell death is important to develop novel therapeutics. Our previous study has shown that triptolide, a diterpene triepoxide, inhibits the growth of pancreatic cancer cells in vitro and prevents tumor growth in vivo. However, the mechanism by which triptolide kills pancreatic cancer cells was not known, hence, this study aimed at elucidating it. Our study reveals that triptolide kills diverse types of pancreatic cancer cells by two different pathways; it induces caspase-dependent apoptotic death in some cell lines and death via a caspase-independent autophagic pathway in the other cell lines tested. Triptolide-induced autophagy requires autophagy-specific genes, atg5 or beclin 1 and its inhibition results in cell death via the apoptotic pathway, whereas inhibition of both autophagy and apoptosis rescues triptolide-mediated cell death. Our study shows for the first time that induction of autophagy by triptolide has a pro-death role in pancreatic cancer cells. Since triptolide kills diverse pancreatic cancer cells by different mechanisms, it makes an attractive chemotherapeutic agent for future use against a broad spectrum of pancreatic cancers.

Original languageEnglish (US)
Pages (from-to)997-998
Number of pages2
JournalAutophagy
Volume6
Issue number7
DOIs
StatePublished - Oct 1 2010

Bibliographical note

Funding Information:
National Institutes of Health grants CA124723, CA131663 (to A.K.S.).

Keywords

  • Apoptosis
  • Caspase-3
  • Pancreatic cancer
  • Triptolide

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