INVESTIGADORES
ALVAREZ Elida Maria Del Carmen
artículos
Título:
Gemcitabine Induces the VMP1-Mediated
Autor/es:
PARDO R; LO RÉ A; ARCHANGE C; ROPOLO A; PAPADEMETRIO D; GONZALEZ C; ALVAREZ E; IOVANNA J; VACCARO M
Revista:
PANCREATOLOGY
Editorial:
KARGER
Referencias:
Año: 2010 vol. 10 p. 19 - 26
ISSN:
1424-3903
Resumen:
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.
in gemcitabine-treated cancer cells.
Conclusions: The VMP1- autophagy pathway promotes apoptosis in pancreatic cancer
cells and mediates gemcitabine-induced cytotoxicity.
cells and mediates gemcitabine-induced cytotoxicity.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.
in gemcitabine-treated cancer cells.
Conclusions: The VMP1- autophagy pathway promotes apoptosis in pancreatic cancer
cells and mediates gemcitabine-induced cytotoxicity.
cells and mediates gemcitabine-induced cytotoxicity.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.
in gemcitabine-treated cancer cells.
Conclusions: The VMP1- autophagy pathway promotes apoptosis in pancreatic cancer
cells and mediates gemcitabine-induced cytotoxicity.
cells and mediates gemcitabine-induced cytotoxicity.