Targeting Metabolism to Induce Cell Death in Cancer Cells and Cancer Stem Cells

Figure 1

Metabolic adaptations of cancer cells. Glucose and glutamine are the 2 major substrates used by cancer cells. Glucose is imported into the cells through glucose transporters (GLUT) where it is phosphorylated by Hexokinase (HK). It will then be either metabolized through glycolysis or diverted to the pentose phosphate pathway (PPP). Glucose-derived pyruvate is mainly converted into lactate in cancer cells instead of being imported into mitochondria to be oxidized in acetyl CoA to support mitochondrial energy production. MYC enables cancer cells to maximize glutamine uptake from the extracellular space through the upregulation of the glutamine transporter. Once glutamine enters the cell, it can be metabolized through glutaminolysis to provide glutamate. The transamination of glutamate to αKG will feed the TCA cycle (adapted from Vander-Heiden et al. [9]). αKG: α-KetoGlutarate; TCA: tricarboxylic acid cycle; PDH: pyruvate dehydrogenase; LDH: lactate dehydrogenase; PDK: PDH-kinase; PK: pyruvate kinase; PEP: phosphoenolpyruvate; GLS: glutamine synthase; SDH: succinate dehydrogenase; FH: fumarate hydratase; 2-HG: 2D-hydroxyGlutarate; IDH: isocitrate dehydrogenase; HK: hexokinase; GAPDH: glyceraldehyde 3-phosphate dehydrogenase.