Yuen-Li Chung1, Helen Troy1, Ian
R. Judson2, John R. Griffiths3, Martin O. Leach1,
Thomas R. Eykyn1
1CR-UK and ESPRC Cancer Imaging Centre,
Institute of Cancer Research, Sutton, Surrey, United Kingdom; 2CR-UK
Centre for Cancer Therapeutics, Institute of Cancer Research, Sutton, Surrey,
United Kingdom; 3Cancer Research UK Cambridge Research Institute,
Cambridge, United Kingdom
Dichloroacetate
(DCA) is a pyruvate dehydrogenase kinase (PDK) inhibitor and is found to be
an anti-cancer agent. The aim of this work was to study the mechanism of
action of DCA and to develop a non-invasive biomarker for response following
PDK inhibition. DCA treatment caused G1 arrest and a dramatic drop in the
conversion of hyerpolarised 13C-labelled pyruvate to lactate. 1H-MRS of the
culture media of DCA-treated cells also showed a reduction in steady state
eupolarised lactate production and increased alanine uptake. These changes have potential as non-invasive
biomarkers of drug action. DCA treatment also altered phospholipid
metabolism, which could provide further biomarkers of response.
Keywords