Abstract
Inhibition of glucose metabolism in pancreatic cancer induces cytotoxicty via metabolic oxidative stress
Journal of the American College of Surgeons, Vol.199(3), pp.24-24
2004
DOI: 10.1016/j.jamcollsurg.2004.05.037
Abstract
Introduction: Glucose metabolism as assessed by of 18FDG PET imaging provides prognostic information in patients with pancreatic cancer (J. Gastro. Surg. 7:953, 2003). Based on previous studies (Cancer Res. 63:3413, 2003), we hypothesized that inhibition of glucose metabolism in pancreatic cancer cells would increase cell killing via oxidative stress resulting in profound disruptions in thiol metabolism. 2-deoxy-D-glucose (2DG) is a relatively non-toxic analog of glucose that competes with glucose for most metabolic pathways resulting in a chemically induced state of glucose deprivation.
Methods: MIA PaCa-2 human pancreatic cancer cells were exposed to 2DG (2–10 mM) with and without the thiol antioxidant N-acetylcysteine (NAC; 20 mM) and survival determined by clonogenic cell survival assay. Cells were assayed for total glutathione, reduced glutathione and glutathione disulfide (GSSG), while cysteine and NAC were determined by HPLC.
Results: 2DG decreased cell survival (71–84%) in a dose-dependent fashion. Treatment with 2DG also caused a 2-fold increase in metabolic oxidative stress as measured by GSSG accumulation. Simultaneous administration of NAC protected MIA PaCa-2 cells against the cytotoxic effects of 2DG as well as reversing 2DG-induced decreases in glutathione content, and augmenting intracellular cysteine.
Conclusions: These results support the hypothesis that 2DG exposure causes cytotoxicity in human pancreatic cancer cells via disruptions in thiol metabolism resulting from metabolic oxidative stress. Support: DK60618, CA66081.
Details
- Title: Subtitle
- Inhibition of glucose metabolism in pancreatic cancer induces cytotoxicty via metabolic oxidative stress
- Creators
- Mitchell C. Coleman - University of IowaSusan A. Walsh - University of IowaLing Li - University of IowaMarilyn M. Hinkhouse - University of IowaDouglas R. Spitz - University of IowaJoseph Cullen - University of Iowa
- Resource Type
- Abstract
- Publication Details
- Journal of the American College of Surgeons, Vol.199(3), pp.24-24
- Publisher
- Elsevier Inc
- DOI
- 10.1016/j.jamcollsurg.2004.05.037
- ISSN
- 1072-7515
- eISSN
- 1879-1190
- Language
- English
- Date published
- 2004
- Academic Unit
- Pathology; Orthopedics and Rehabilitation; Fraternal Order of Eagles Diabetes Research Center; Surgery; Radiology; Radiation Oncology
- Record Identifier
- 9984305998502771
Metrics
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