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

Damon C Shutt; M Sue O'Dorisio; Nukhet Aykin-Burns; Douglas R Spitz

doi:10.4161/cbt.9.11.11632

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

Journal article

Open access

Peer reviewed

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

Damon C Shutt, M Sue O'Dorisio, Nukhet Aykin-Burns and Douglas R Spitz

Cancer biology & therapy, Vol.9(11), pp.853-861

06/01/2010

DOI: 10.4161/cbt.9.11.11632

PMCID: PMC3215774

PMID: 20364116

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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.

Catalase - pharmacology

Free Radical Scavengers - pharmacology

Immunohistochemistry

Humans

Glycoproteins - metabolism

Neurons - cytology

Polyethylene Glycols - chemistry

Stem Cells - metabolism

Antigens, CD - metabolism

Dose-Response Relationship, Drug

Tubulin - metabolism

Peptides - metabolism

Time Factors

Deoxyglucose - pharmacology

Neurons - metabolism

Neurons - drug effects

Neuroblastoma - pathology

Antimetabolites - pharmacology

Cell Line

Cell Survival - drug effects

Superoxide Dismutase - pharmacology

Antioxidants - pharmacology

AC133 Antigen

Superoxide Dismutase - chemistry

Transglutaminases - metabolism

Acetylcysteine - pharmacology

Cell Line, Tumor

Stem Cells - drug effects

Neuroblastoma - metabolism

GTP-Binding Proteins

Oxidative Stress - drug effects

Catalase - chemistry

Details

Title: Subtitle: 2-deoxy-D-glucose induces oxidative stress and cell killing in human neuroblastoma cells
Creators: Damon C Shutt - Free Radical and Radiation Biology Program, Department of Radiation Oncology and Division of Hematology and Oncology, Department of Pediatrics, Holden Comprehensive Cancer Center, University of Iowa Carver College of Medicine, Iowa City, IA, USA. damon-shutt@uiowa.edu
M Sue O'Dorisio
Nukhet Aykin-Burns
Douglas R Spitz
Resource Type: Journal article
Publication Details: Cancer biology & therapy, Vol.9(11), pp.853-861
DOI: 10.4161/cbt.9.11.11632
PMID: 20364116
PMCID: PMC3215774
NLM abbreviation: Cancer Biol Ther
ISSN: 1538-4047
eISSN: 1555-8576
Publisher: United States
Grant note: P30 CA086862-01 / NCI NIH HHS R01CA100045 / NCI NIH HHS R01 CA133114-01A1 / NCI NIH HHS R01 CA100045-04S1 / NCI NIH HHS R01CA100045-S1 / NCI NIH HHS R01CA133114 / NCI NIH HHS P30CA086862 / NCI NIH HHS R01 CA133114 / NCI NIH HHS R01 CA100045-02 / NCI NIH HHS P30 CA086862 / NCI NIH HHS R01 CA100045 / NCI NIH HHS
Language: English
Date published: 06/01/2010
Academic Unit: Stead Family Department of Pediatrics; Pathology; Radiation Oncology; Nursing
Record Identifier: 9984047858102771

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