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2-deoxy-D-glucose induces oxidative stress and cell killing in human neuroblastoma cells
| Content Provider | Scilit |
|---|---|
| Author | O'Dorisio, M. Sue Shutt, Damon Aykin-Burns, Nukhet Spitz, Douglas |
| Copyright Year | 2010 |
| Description | Malignant cells have a demonstrably greater sensitivity to glucose deprivation-induced cytotoxicity than normal cells (Biochem. J. 418:29). 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. |
| Related Links | https://www.tandfonline.com/doi/pdf/10.4161/cbt.9.11.11632?needAccess=true https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3215774/pdf |
| Ending Page | 861 |
| Page Count | 9 |
| Starting Page | 853 |
| ISSN | 15384047 |
| e-ISSN | 15558576 |
| DOI | 10.4161/cbt.9.11.11632 |
| Journal | Cancer Biology & Therapy |
| Issue Number | 11 |
| Volume Number | 9 |
| Language | English |
| Publisher | Informa UK Limited |
| Publisher Date | 2010-06-01 |
| Access Restriction | Open |
| Subject Keyword | Toxicology Glucose Deprivation Oxidative Stress Clonogenic Survival N-acetyl Cysteine Superoxide Dismutase Catalase I-cells N-cells S-cells Sk-n-sh Sh-sy5y |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cancer Research Pharmacology Molecular Medicine Oncology |
