Dichloroacetate (DCA) and Cancer: An Overview towards Clinical Applications

Figure 3

Other proposed mechanisms of action of DCA. DCA’s main mechanism is to inhibit pyruvate dehydrogenase kinase (PDK), leading to pyruvate dehydrogenase (PDH) activation and fostering oxidative phosphorylation (1). DCA also increases each Krebs cycle intermediate concentration (2) [87]. DCA induces cell toxicity via de novo synthesis of CoA (3) [88]. DCA may antagonize acetate (4) [90]. DCA modulates intracellular acidification (5) [93, 94]. DCA inhibits Na-K-2Cl cotransporter (6) [96]. DCA downregulates gene and protein expression of ABC transporters (7) [97]. DCA reduces the expression of self-renewal-related genes and affects cancer stem cell fraction (8) [99].