Cytotoxicity, radiosensitization, and chemosensitization of tumor cells by 2-deoxy-D-glucose in vitro.
The glucose analog 2-deoxy-D-glucose (2-DG), an inhibitor of glucose transport and glycolytic ATP production, is the most widely investigated metabolic inhibitor for targeting glucose metabolism. Besides depleting energy in cells, 2-DG has also been found to alter N-linked glycosylation leading to unfolded protein responses and induce changes in gene expression and phosphorylation status of proteins involved in signaling, cell cycle control, DNA repair, calcium influx, and apoptosis. Inhibition of cell proliferation and induction of apoptosis have been observed as cytotoxic effects in a wide variety of tumor cells in vitro, while sensitization of tumor cells to ionizing radiation and certain chemotherapeutic drugs is associated with enhanced mitotic as well as apoptotic cell death induced by the primary therapeutic agent. Therefore, there has been a considerable amount of interest in developing 2-DG as a therapeutic agent or adjuvant in the radiotherapy and chemotherapy of tumors.
Dwarakanath
B S
BS
Division of Radiation Biosciences, Institute of Nuclear Medicine and Allied Sciences, New Delhi, India.
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D003847:Deoxyglucose / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D009369:Neoplasms / Q000378:metabolism*; D011836:Radiation Tolerance / Q000502:physiology*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D011878:Radiotherapy
D000970:Antineoplastic Agents; D011838:Radiation-Sensitizing Agents; D003847:Deoxyglucose