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2-deoxyglucose sensitizes melanoma cells to TRAIL-induced apoptosis which is reduced by mannose.
- Source :
-
Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2010 Oct 15; Vol. 401 (2), pp. 293-9. Date of Electronic Publication: 2010 Sep 17. - Publication Year :
- 2010
-
Abstract
- While melanoma cell lines use aerobic glycolysis, addition of a competitive inhibitor such as 2-deoxyglucose (2DG) by itself achieved only modest killing. To overcome high levels of pro-survival proteins in melanoma cells, 2DG or glucose deprivation (GD) was combined with tumor necrosis factor-related apoptosis inducing-ligand (TRAIL). TRAIL treatment by itself also only induced modest killing, but combining TRAIL with 2DG or GD triggered a synergistic pro-apoptotic response in melanoma lines but not melanocytes. In melanoma cells, there was cleavage of caspases 3, 8 and Bid. Killing by combination treatments was completely blocked by a pan-caspase inhibitor, z-VAD. Mechanistically, 2DG and GD enhanced surface levels for both death receptors (DR4 and DR5); which was accompanied by reductions in levels of Mcl-1, Bcl-2 and survivin. Mannose pre-treatment reduced enhanced killing by combination treatments, accompanied by reduced DR5 levels. These results indicate melanoma cells in which there is altered glucose-related metabolomics can be exploited by interfering with glucose metabolism in combination with TRAIL; thereby overcoming the notorious death resistance of melanoma. Thus, a new therapeutic window is open for future clinical trials using agents targeting the glucose-related metabolome, in combination with agents triggering death receptors in patients with melanoma.<br /> (Copyright © 2010 Elsevier Inc. All rights reserved.)
Details
- Language :
- English
- ISSN :
- 1090-2104
- Volume :
- 401
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Biochemical and biophysical research communications
- Publication Type :
- Academic Journal
- Accession number :
- 20851102
- Full Text :
- https://doi.org/10.1016/j.bbrc.2010.09.054