Journal article
2-Deoxy- d-glucose causes cytotoxicity, oxidative stress, and radiosensitization in pancreatic cancer
Free radical biology & medicine, Vol.44(3), pp.322-331
2008
DOI: 10.1016/j.freeradbiomed.2007.08.032
PMID: 18215740
Abstract
Glucose metabolism as assessed by
18FDG PET imaging provides prognostic information in patients with pancreatic cancer but the implications of manipulating glucose metabolism for therapeutic purposes are unknown. Based on previous results with other cancer cell types, we hypothesized that inhibition of glucose metabolism in pancreatic cancer cells would cause cell killing via oxidative stress resulting from disruptions in thiol metabolism. 2-Deoxy-
d-glucose (2DG), a chemical inhibitor of glucose metabolism, and glucose deprivation induced cytotoxicity in human pancreatic cancer cells in a time-and dose-dependent manner as well as causing significant increases in metabolic oxidative stress as measured by increased glutathione disulfide accumulation and NADP
+/NADPH ratios. Simultaneous administration of the thiol antioxidant
N-acetylcysteine protected pancreatic cancer cells against the c-ytotoxic effects of 2DG as well as reversing 2DG-induced glutathione disulfide accumulation and augmenting intracellular cysteine pools. In nude mice with heterotopic pancreatic tumors, the combination of 2DG and ionizing radiation resulted in greater inhibition of tumor growth and increased survival, relative to either agent alone. These results support the hypothesis that inhibiting glucose metabolism causes cytotoxicity in human pancreatic cancer cells via metabolic oxidative stress and disruptions in thiol metabolism. These results also support the speculation that inhibitors of glucose metabolism can be used in combination with classical oxidative stress-inducing agents (such as ionizing radiation) to enhance therapeutic responses in pancreatic cancer.
Details
- Title: Subtitle
- 2-Deoxy- d-glucose causes cytotoxicity, oxidative stress, and radiosensitization in pancreatic cancer
- Creators
- Mitchell C Coleman - Department of Radiation Oncology, University of Iowa, Iowa City, IA 52242, USACarla R Asbury - College of Medicine, University of Iowa, Iowa City, IA 52242, USADavid Daniels - College of Medicine, University of Iowa, Iowa City, IA 52242, USAJuan Du - Department of Radiation Oncology, University of Iowa, Iowa City, IA 52242, USANukhet Aykin-Burns - Department of Radiation Oncology, University of Iowa, Iowa City, IA 52242, USABrian J Smith - Holden Comprehensive Cancer Center, Iowa City, IA 52242, USALing Li - Department of Radiation Oncology, University of Iowa, Iowa City, IA 52242, USADouglas R Spitz - Department of Radiation Oncology, University of Iowa, Iowa City, IA 52242, USAJoseph J Cullen - Department of Radiation Oncology, University of Iowa, Iowa City, IA 52242, USA
- Resource Type
- Journal article
- Publication Details
- Free radical biology & medicine, Vol.44(3), pp.322-331
- DOI
- 10.1016/j.freeradbiomed.2007.08.032
- PMID
- 18215740
- NLM abbreviation
- Free Radic Biol Med
- ISSN
- 0891-5849
- eISSN
- 1873-4596
- Publisher
- Elsevier Inc
- Language
- English
- Date published
- 2008
- Academic Unit
- Pathology; Biostatistics; Orthopedics and Rehabilitation; Surgery; Radiation Oncology; Holden Comprehensive Cancer Center
- Record Identifier
- 9983997307502771
Metrics
24 Record Views