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Autophagy sustains the survival of human pancreatic cancer PANC-1 cells under extreme nutrient deprivation conditions

Title
Autophagy sustains the survival of human pancreatic cancer PANC-1 cells under extreme nutrient deprivation conditions
Author
배옥남
Keywords
Autophagy; PANC-1; Extreme nutrient deprivation; Apoptosis; Survival; MITOCHONDRIAL DYSFUNCTION; TUMOR-GROWTH; APOPTOSIS; DEATH; INHIBITION; METABOLISM; TOLERANCE; THERAPY; FUSION; ROLES
Issue Date
2015-07
Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
Citation
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, v. 463, No. 3, Page. 205-210
Abstract
Pancreatic ductal adenocarcinomas are an extremely aggressive and devastating type of cancer with high mortality. Given the dense stroma and poor vascularization, accessibility to nutrients is limited in the tumor microenvironment Here, we aimed to elucidate the role of autophagy in promoting the survival of human pancreatic cancer PANC-1 cells exposed to nutrient-deprived media (NDM) lacking glucose, amino acids, and serum. NDM inhibited Akt activity and phosphorylation of p70 S6K, and induced AMPK activation and mitochondrial depolarization. NDM also time-dependently increased LC3-II accumulation, number of GFP-LC3 puncta, and colocalization between GFP-LC3 and lysosomes. These results suggested that autophagy was progressively activated through Akt- and AMPK-mTOR pathway in nutrient-deficient PANC-1 cells. Autophagy inhibitors (chloroquine and wortmannin) or silencing of Atg5 augmented PANC-1 cell death in NDM. In cells exposed to NDM, chloroquine and wortmannin induced apoptosis and Z-VAD-fmk inhibited cytotoxicity of these inhibitors. These data demonstrate that autophagy is antiapoptotic and sustains the survival of PANC-1 cells following extreme nutrient deprivation. Autophagy modulation may be a viable therapeutic option for cancer cells located in the core of solid tumors with a nutrient-deficient microenvironment. (C) 2015 Elsevier Inc. All rights reserved.
URI
https://www.sciencedirect.com/science/article/pii/S0006291X15009365?_rdoc=1&_fmt=high&_origin=gateway&_docanchor=&md5=b8429449ccfc9c30159a5f9aeaa92ffbhttp://hdl.handle.net/20.500.11754/36933
ISSN
0006-291X; 1090-2104
DOI
10.1016/j.bbrc.2015.05.022
Appears in Collections:
COLLEGE OF PHARMACY[E](약학대학) > PHARMACY(약학과) > Articles
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