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. and IAP.
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 humanpancreatic 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. and IAP.
Authors: Tetyana V Bagnyukova; Ilya G Serebriiskii; Yan Zhou; Elizabeth A Hopper-Borge; Erica A Golemis; Igor Astsaturov Journal: Cancer Biol Ther Date: 2010-11-01 Impact factor: 4.742
Authors: Andrea E Lo Ré; Maite G Fernández-Barrena; Luciana L Almada; Lisa D Mills; Sherine F Elsawa; George Lund; Alejandro Ropolo; Maria I Molejon; Maria I Vaccaro; Martin E Fernandez-Zapico Journal: J Biol Chem Date: 2012-04-25 Impact factor: 5.157
Authors: Naser M Ali; Stefania Niada; Anna T Brini; Mark R Morris; Sathishkumar Kurusamy; Abdullah Alholle; David Huen; Cristina R Antonescu; Franck Tirode; Vaiyapuri Sumathi; Farida Latif Journal: J Pathol Date: 2018-12-27 Impact factor: 7.996