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. 2015 Nov 2;7(3):2910–2920. doi: 10.18632/oncotarget.6272

Figure 6. Mechanism by which DCA controls proliferation of glycolytic cancer cells.

Figure 6

Highly glycolytic cancer cells exhibiting a Warburg phenotype ferment large amounts of glucose into lactate even in the presence of oxygen. This phenomenon allows rapid ATP production and provides precursors for biosynthetic processes promoting cell proliferation. By alleviating PDH inhibition by PDK, DCA fosters the conversion of pyruvate into acetyl-CoA and activates mitochondrial respiration. The consequent allosteric inhibition of glycolysis by ATP reduces glucose consumption and glycolytic intermediates levels, thereby decreasing the flux of the pentose phosphate pathway along with cellular proliferation. PDH, Pyruvate Dehydrogenase. PDK, Pyruvate Dehydrogenase Kinase. G6P, Glucose-6-phosphate. NAD, Nicotinamide Adenine Dinucleotide. NADP, Nicotinamide Adenine Dinucleotide Phosphate. Glut, Glucose Transporter. MCT4, Monocarboxylate Transporter 4.