2-Deoxy-d-glucose activates autophagy via endoplasmic reticulum stress rather than ATP depletion
- 1 July 2010
- journal article
- research article
- Published by Springer Science and Business Media LLC in Cancer Chemotherapy and Pharmacology
- Vol. 67 (4), 899-910
- https://doi.org/10.1007/s00280-010-1391-0
Abstract
The glucose analog and glycolytic inhibitor 2-deoxy-d-glucose (2-DG), which is currently under clinical evaluation for targeting cancer cells, not only blocks glycolysis thereby reducing cellular ATP, but also interferes with N-linked glycosylation, which leads to endoplasmic reticulum (ER) stress and an unfolded protein response (UPR). Both bioenergetic challenge and ER stress have been shown to activate autophagy, a bulk cellular degradation process that plays either a pro- or anti-death role. Here, we investigate which pathway 2-DG interferes with that activates autophagy and the role of this process in modulating 2-DG-induced toxicity.Keywords
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