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.
Keywords: Angiogenesis, Autophagy, Apoptosis, Cancer, Glycolysis.
