The Role of Akt Pathway Signaling in Glucose Metabolism and Metabolic Oxidative Stress

  • Andrean L. Simons
  • Kevin P. Orcutt
  • Joshua M. Madsen
  • Peter M. Scarbrough
  • Douglas R. Spitz
Chapter
Part of the Oxidative Stress in Applied Basic Research and Clinical Practice book series (OXISTRESS)

Abstract

Glucose metabolism plays an important role in hydroperoxide detoxification and the inhibition of glucose metabolism has been shown to increase prooxidant production and cytotoxicity in cancer cells. Increased Akt pathway signaling has been shown to be directly correlated with increased rates of glucose metabolism observed in cancer cells versus normal cells. These observations have led to the proposal that inhibition of Akt signaling would inhibit glycolysis and increase hydroperoxide production which would preferentially kill tumor cells versus normal cells via oxidative stress. The current study shows that inhibition of the Akt pathway inhibits glucose consumption and induces parameters indicative of oxidative stress such as glutathione disulfide (%GSSG) and thioredoxin reductase (TR) activity in human head and neck cancer (HNSCC) cells. A theoretical model to explain the results is presented and implications for the use of Akt pathway inhibitors in combination with glycolytic inhibitors and/or manipulations that increase prooxidant production are discussed.

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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Andrean L. Simons
    • 1
    • 2
  • Kevin P. Orcutt
    • 2
  • Joshua M. Madsen
    • 2
  • Peter M. Scarbrough
    • 2
  • Douglas R. Spitz
    • 2
  1. 1.Department of Pathology, Holden Comprehensive Cancer CenterThe University of IowaIowa CityUSA
  2. 2.Free Radical and Radiation Biology Program, Department of Radiation Oncology, Holden Comprehensive Cancer CenterThe University of IowaIowa CityUSA

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