| 2-deoxyglucose sensitizes melanoma cells to TRAIL-induced apoptosis which is reduced by mannose. | |
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MedLine Citation:
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PMID: 20851102 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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J-Z Qin; H Xin; B J Nickoloff |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-09-17 |
Journal Detail:
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Title: Biochemical and biophysical research communications Volume: 401 ISSN: 1090-2104 ISO Abbreviation: Biochem. Biophys. Res. Commun. Publication Date: 2010 Oct |
Date Detail:
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Created Date: 2010-10-18 Completed Date: 2010-11-30 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0372516 Medline TA: Biochem Biophys Res Commun Country: United States |
Other Details:
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Languages: eng Pagination: 293-9 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 Elsevier Inc. All rights reserved. |
Affiliation:
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Department of Pathology, Loyola University Medical Center, Maywood, IL 60153-5385, United States. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Apoptosis
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drug effects* Cell Line, Tumor Deoxyglucose / pharmacology* Drug Resistance, Neoplasm / drug effects* Glucose / deficiency, pharmacology Humans Mannose / pharmacology* Melanoma / metabolism* TNF-Related Apoptosis-Inducing Ligand / pharmacology* |
| Chemical | |
Reg. No./Substance:
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0/TNF-Related Apoptosis-Inducing Ligand; 154-17-6/Deoxyglucose; 31103-86-3/Mannose; 50-99-7/Glucose |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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