Dichloroacetate treatment resulted in a dramatic drop in the conversion of hyperpolarised 1-13 C labelled pyruvate to lactate in human colon carcinoma cells

INTRODUCTION: Dichloroacetate (DCA) is a pyruvate dehydrogenase kinase (PDK) inhibitor and is found to be an anti-cancer agent [1]. It causes the activation of pyruvate dehydrogenase (PDH) and increased glucose oxidation by promoting the influx of acetyl-CoA into the mitochondria and the Krebs cycle [1]. The hyperpolarised C experiment measures the conversion of labelled pyruvate to labelled lactate which has been shown to be proportional to lactate dehydrogenase activity and the availability of cellular NADH, the enzyme co-factor [2]. Conversely, steady state measurements of eupolarised (i.e. unlabelled) lactate production report on the overall flux through glycolysis.