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

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 and Douglas R Spitz
Oxidative Stress in Cancer Biology and Therapy, pp.21-46
Oxidative Stress in Applied Basic Research and Clinical Practice, Humana Press
10/21/2011
DOI: 10.1007/978-1-61779-397-4_2

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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.
Epidermal Growth Factor Receptor Epidermal Growth Factor Receptor Overexpression Epidermal Growth Factor Receptor Signaling FaDu Cell Human Epidermal Growth Factor Receptor

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