2-Deoxy-D-Glucose: A Glycolysis Inhibitor in the Treatment of Cancer

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Cancer involves abnormal and rapid cell growth, which requires an increased energy supply for proliferating cells. As the demand for glucose rises in cancer cells, the expression and activity of glucose transporters (GLUTs) also increase to facilitate higher cellular glucose uptake. Cancer cells tend to shift their glucose metabolic pathway from mitochondrial oxidative phosphorylation towards aerobic glycolysis. 2-Deoxy-D-glucose competes with glucose and involves aerobic glycolysis. It leads to the inhibition of HK and PGI, diminishes ATP production, and induces apoptosis. Further, the increase in the AMP/ATP ratio promotes the AMPK signaling, downregulating VEGF, and leading to angiogenesis inhibition and autophagy. As the structural mimic of mannose, 2-DG interferes with the N-linked glycosylation, leading to ER stress, and triggering the mitochondrial apoptotic pathway. 2-DG has been employed as an antiproliferative, antiangiogenic, and antimetastatic drug by being involved in the energy metabolic pathway. Combination therapy shows improved results and reduces chemotherapeutic drug resistance. In this chapter, we will discuss the Warburg effect, the role of 2-DG in the inhibition of aerobic glycolysis, and how 2- DG inhibits the various other cancer hallmarks in energy metabolic pathway. Also, reports on cancer treatment as well as cancer cell-imaging and risks associated with chronic exposure are discussed.