Elsevier

Pancreatology

Volume 10, Issue 1, April 2010, Pages 19-26
Pancreatology

Gemcitabine Induces the VMP1 -Mediated Autophagy Pathway to Promote Apoptotic Death in Human Pancreatic Cancer Cells

https://doi.org/10.1159/000264680Get rights and content

Abstract

Background/Aim: Autophagy is a degradation process of cytoplasmic cellular constituents. We have described the vacuole membrane protein-1 (VMP1) whose expression triggers autophagy in mammalian cells. The aim of this study was to analyze the role of autophagy in human pancreatic cancer cell death. Methods/Results: Here we show that gemcitabine, the standard chemotherapy for pancreatic cancer, induced autophagy in PANC-1 and MIAPaCa-2 cells, as evidenced by the accumulation of acidic vesicular organelles, the recruitment of microtubule-associated protein-1 light chain-3, and electron microscopy. In addition, gemcitabine treatment induced early expression of VMP1 in cancer cells. Gemcitabine also induced apoptosis detected by morphology, annexin V-positive cells, and cleavage of caspase-3. Surprisingly, 3-methyladenine, an autophagy inhibitor, decreased apoptosis in gemcitabine-treated cells, showing that autophagy leads to cancer cell apoptotic death. Finally, VMP1 knockdown decreased autophagy and apoptosis in gemcitabine-treated cancer cells. Conclusions: The VMP1-autophagy pathway promotes apoptosis in pancreatic cancer cells and mediates gemcitabine-induced cytotoxicity.

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  • Cited by (0)

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    Maria I. Vaccaro Department of Physiology, School of Medicine University of Buenos Aires, 2155 Paraguay p7 Buenos Aires C1121ABG (Argentina) Tel. +54 11 5950 9500, ext. 2127, Fax +54 11 4433 4539

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