2-Deoxy-d-glucose enhances TRAIL-induced apoptosis in human gastric cancer cells through downregulating JNK-mediated cytoprotective autophagy

2-Deoxy-d-glucose enhances TRAIL-induced apoptosis in human gastric cancer cells through... Purpose TNF-related apoptosis-inducing ligand (TRAIL) resistance significantly limits its use in clinical practice. It has been reported that 2-deoxy-d -glucose (2-DG) can enhance TRAIL’s cytotoxicity. Our studies were designed to investigate the mechanisms of 2-DG reversing TRAIL resistance therapy in gastric cancer cells. Methods Gastric cancer cells (MGC803, SGC7901) were treated with 2-DG and TRAIL. Cell viability was determined by CCK-8 assay and detection of apoptosis by flow cytometry. Autophagic and apoptosis protein expression and c-Jun NH2- terminal kinase (JNK) phosphorylation were determined by Western blotting. Autophagy response and JNK activities were inhibited by specific inhibitor, 3MA or SP600125, respectively. LDH release assay was used to detect cytotoxicity. Results We confirmed that TRAIL triggered an autophagic response in TRAIL-resistant gastric cancer cells, MGC803 and SGC7901, and depended on JNK activation. Blocking autophagy or JNK activation with specific inhibitor, 3MA or SP600125, potentiated cell death and caspase-3 activation. Furthermore, we confirmed that 2-DG inhibited the viability of gastric cancer cells, phosphorylation of JNK induced by TRAIL and increased gastric cancer cells to TRAIL-induced apoptosis. Conclusions Taken together, we show that 2-DG can sensitize TRAIL-induced apoptosis, at least in part, through suppress- ing JNK-mediated cytoprotective autophagic signaling in MGC803 and SGC7901cells. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Cancer Chemotherapy and Pharmacology Springer Journals

2-Deoxy-d-glucose enhances TRAIL-induced apoptosis in human gastric cancer cells through downregulating JNK-mediated cytoprotective autophagy

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Publisher
Springer Berlin Heidelberg
Copyright
Copyright © 2018 by Springer-Verlag GmbH Germany, part of Springer Nature
Subject
Medicine & Public Health; Oncology; Pharmacology/Toxicology; Cancer Research
ISSN
0344-5704
eISSN
1432-0843
D.O.I.
10.1007/s00280-018-3526-7
Publisher site
See Article on Publisher Site

Abstract

Purpose TNF-related apoptosis-inducing ligand (TRAIL) resistance significantly limits its use in clinical practice. It has been reported that 2-deoxy-d -glucose (2-DG) can enhance TRAIL’s cytotoxicity. Our studies were designed to investigate the mechanisms of 2-DG reversing TRAIL resistance therapy in gastric cancer cells. Methods Gastric cancer cells (MGC803, SGC7901) were treated with 2-DG and TRAIL. Cell viability was determined by CCK-8 assay and detection of apoptosis by flow cytometry. Autophagic and apoptosis protein expression and c-Jun NH2- terminal kinase (JNK) phosphorylation were determined by Western blotting. Autophagy response and JNK activities were inhibited by specific inhibitor, 3MA or SP600125, respectively. LDH release assay was used to detect cytotoxicity. Results We confirmed that TRAIL triggered an autophagic response in TRAIL-resistant gastric cancer cells, MGC803 and SGC7901, and depended on JNK activation. Blocking autophagy or JNK activation with specific inhibitor, 3MA or SP600125, potentiated cell death and caspase-3 activation. Furthermore, we confirmed that 2-DG inhibited the viability of gastric cancer cells, phosphorylation of JNK induced by TRAIL and increased gastric cancer cells to TRAIL-induced apoptosis. Conclusions Taken together, we show that 2-DG can sensitize TRAIL-induced apoptosis, at least in part, through suppress- ing JNK-mediated cytoprotective autophagic signaling in MGC803 and SGC7901cells.

Journal

Cancer Chemotherapy and PharmacologySpringer Journals

Published: Jan 31, 2018

References

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