Glucose deprivation-induced metabolic oxidative stress and cancer therapy
Year: 2009
Type: article
Abstract: Cancer cells (vs. normal cells) demonstrate evidence of oxidative stress, increased glycolysis, and increased pentose cycle activity. The oxidative stress in cancer cells has been hypothesized to arise from mitochondrial dysfunction leading to increased levels of hydroperoxides, and cancer cells have been proposed to compensate for this defect by increasing glucose metabolism. Glucose metabolism has also been shown to play a role in hydroperoxide detoxification via the formation of pyruvate (from glycolysis) and NADPH (from the pentose cycle). Furthermore, in cancer cells, glucose deprivation as well as treatment with 2-deoxyglucose (2 DG) has been shown to induce oxidative stress and cytotoxicity. Additionally, transformed cells have been shown to be more susceptible to glucose deprivation (and 2DG-)-induced cytotoxicity and oxidative stress than untransformed cells. These results support the hypothesis that cancer cells have a defect in mitochondrial respiration leading to increased steady state levels of O2*- and H2O2, and glucose metabolism is increased to compensate for this defect. The application of these findings to developing cancer therapies using 2DG combined with inhibitors of hydroperoxide metabolism to induce radio/chemosensitization is discussed, as well as the possibility that FDG-PET imaging may predict tumor responses to these therapies.
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: diamond
Awards: The Use of 2-Deoxyglucose in Head and Neck Cancer Therapy, Metabolic Oxidative Stress in Human Cancer Cells, Training Program in Free Radical and Radiation Biology, Oxidative Events in Cancer Therapy, Use of 2-deoxy-D-glucose & PI3K/Akt pathway inhibitors in head & neck cancer ther, Cancer Center Support Grant
OpenAlex ID: W2026167469