DCA – turning on OxPhos

“Inhibition of mitochondrial pyruvate dehydrogenase kinase (PDK) by dichloroacetate may be exploited to reverse the abnormal metabolism of cancer cells from glycolysis to glucose oxidation. As PDK negatively regulates pyruvate dehydrogenase, dichloroacetate indirectly stimulates the pyruvate to acetyl-CoA conversion. Dichloroacetate has been shown to downregulate the aberrantly high mitochondrial membrane potential of cancer cells, increase mitochondrial ROS generation and activate K+ channels in malignant, but not in normal cells143. Dichloroacetate also upregulated the expression of the K+ channel Kv1.5, which is often underexpressed by tumour cells, through the transcription factor nuclear factor of activated T cells (NFAT1). Dichloroacetatenormalized mitochondrial functions were accompanied by reduced proliferation, increased apoptosis and suppressed tumour growth without apparent toxicity, suggesting that the mitochondria–NFAT–Kv axis and PDK represent promising anticancer drug targets”.

Sodium dichloroacetate exhibits anti-leukemic activity in B-chronic lymphocytic leukemia (B-CLL) and synergizes with the p53 activator Nutlin-3

The anti-leukemic activity of sodium dichloroacetate in p53mutated/null cells is mediated by a p53-independent ILF3/p21 pathway

Targeting mitochondria for cancer therapy

738px-Dichloroacetic-acid-2D-skeletal

Sodium dichloroacetate exhibits anti-leukemic activity in B-chronic lymphocytic leukemia (B-CLL) and synergizes with the p53 activator Nutlin-3

Sodium dichloroacetate selectively targets cells with defects in the mitochondrial ETC

Combination of Sulindac and Dichloroacetate Kills Cancer Cells via Oxidative Damage

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