2-deoxy-D-glucose induces oxidative stress and cell killing in human neuroblastoma cells.

Abstract

Malignant cells have a demonstrably greater sensitivity to glucose deprivation-induced cytotoxicity than normal cells. This has been hypothesized to be due to a higher level of reactive oxygen species (ROS) production in cancer cells leading to the increased need for reducing equivalents, produced by glucose metabolism, to detoxify hydroperoxides. Because complete glucose deprivation cannot be achieved in vivo, it has been proposed that agents that antagonize glucose metabolism, such as 2-deoxy-D-glucose (2DG), can mimic in vitro glucose deprivation that selectively kills cancer cells by oxidative stress. To test this hypothesis, neuroblastoma cell lines were treated with 2DG and the effects on clonogenic survival and the distribution of cellular phenotypes among surviving colonies was determined. The results showed that all three major cell types found in neuroblastoma (Schwann, Neuronal and Intermediate) were sensitive to 2DG-induced clonogenic cell killing. Furthermore, treatment with the thiol antioxidant, N-acetyl cysteine or with polyethylene glycol-conjugated superoxide dismutase and catalase, protected neuroblastoma cells from 2DG-induced cell killing. Finally normal non-immortalized neural precursor cells were relatively resistant to 2DG-induced cell killing when compared to neuroblastoma cell lines. These results support the hypothesis that inhibitors of glucose metabolism could represent useful adjuvants in the treatment of neuroblastoma by selectively enhancing metabolic oxidative stress.

• Authors: Damon C Shutt, M Sue O'Dorisio, Nukhet Aykin-Burns, Douglas R Spitz
• Journal: Cancer biology & therapy (Cancer Biol Ther) Vol. 9 Issue 11 Pg. 853-61 (Jun 01 2010) ISSN: 1555-8576 [Electronic] United States
• PMID: 20364116 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• AC133 Antigen
• Antigens, CD
• Antimetabolites
• Antioxidants
• Free Radical Scavengers
• Glycoproteins
• Peptides
• TUBB3 protein, human
• Tubulin
• Polyethylene Glycols
• Deoxyglucose
• Catalase
• Superoxide Dismutase
• Protein Glutamine gamma Glutamyltransferase 2
• Transglutaminases
• GTP-Binding Proteins
• Acetylcysteine

Topics

• AC133 Antigen
• Acetylcysteine (pharmacology)
• Antigens, CD (metabolism)
• Antimetabolites (pharmacology)
• Antioxidants (pharmacology)
• Catalase (chemistry, pharmacology)
• Cell Line
• Cell Line, Tumor
• Cell Survival (drug effects)
• Deoxyglucose (pharmacology)
• Dose-Response Relationship, Drug
• Free Radical Scavengers (pharmacology)
• GTP-Binding Proteins
• Glycoproteins (metabolism)
• Humans
• Immunohistochemistry
• Neuroblastoma (metabolism, pathology)
• Neurons (cytology, drug effects, metabolism)
• Oxidative Stress (drug effects)
• Peptides (metabolism)
• Polyethylene Glycols (chemistry)
• Protein Glutamine gamma Glutamyltransferase 2
• Stem Cells (drug effects, metabolism)
• Superoxide Dismutase (chemistry, pharmacology)
• Time Factors
• Transglutaminases (metabolism)
• Tubulin (metabolism)