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A low-dose arsenic-induced p53 protein-mediated metabolic mechanism of radiotherapy protection.

Authors
  • Ganapathy, Suthakar
  • Xiao, Shaowen
  • Yang, Mei
  • Qi, Min
  • Choi, Doo Eun
  • Ha, Chul S
  • Little, John B
  • Yuan, Zhi-Min
Type
Published Article
Journal
Journal of Biological Chemistry
Publisher
American Society for Biochemistry and Molecular Biology
Publication Date
Feb 21, 2014
Volume
289
Issue
8
Pages
5340–5347
Identifiers
DOI: 10.1074/jbc.M113.531020
PMID: 24391088
Source
Medline
Keywords
License
Unknown

Abstract

Radiotherapy is the current frontline cancer treatment, but the resulting severe side effects often pose a significant threat to cancer patients, raising a pressing need for the development of effective strategies for radiotherapy protection. We exploited the distinct metabolic characteristics between normal and malignant cells for a metabolic mechanism of normal tissue protection. We showed that low doses of arsenic induce HIF-1α, which activates a metabolic shift from oxidative phosphorylation to glycolysis, resulting in increased cellular resistance to radiation. Of importance is that low-dose arsenic-induced HIF-1α requires functional p53, limiting the glycolytic shift to normal cells. Using tumor-bearing mice, we provide proof of principle for selective normal tissue protection against radiation injury.

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