NMR-based evaluation of the metabolic profile and response to dichloroacetate of human prostate cancer cells.
Bottom Line: Following the treatment of cells with 50 mm DCA, there was a significant reduction in the lactate/choline, lactate/creatine, lactate/alanine and the combined lactate/(choline + creatine + alanine) ratios in LNCaP-LN3 cells relative to LNCaP cells.No significant changes in metabolite ratios were found in LNCaP cells following DCA treatment.This effect was probably related to the absence of the LDH-B subunit in LNCaP-LN3 cells, and could have a bearing on cancer treatment with DCA and related compounds.
Affiliation: Department of Cardiovascular Science, The Medical School, University of Sheffield, Sheffield, UK.Show MeSH
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Mentions: In the presence of oxygen, normal cells derive most of their energy in the form of ATP from glycolysis, coupled with mitochondrial oxidative phosphorylation, in a process that yields a total of 36 ATP molecules per molecule of glucose consumed, in addition to CO2 and water 8. However, when the supply of oxygen is limited, pyruvate is converted to lactate by a reaction catalysed by lactate dehydrogenase (LDH) (Fig. 1). LDH is a tetrameric enzyme, consisting of different combinations of two subunits (LDH-A and LDH-B, encoded by two different genes) to form five different isoenzymes LDH-1–LDH-5: LDH-B4 (LDH-1); LDH-B3:A1 (LDH-2); LDH-B2:A2 (LDH-3), LDH-B1:A3 (LDH-4) and LDH-A4 (LDH-5) subunits 9,10.
Affiliation: Department of Cardiovascular Science, The Medical School, University of Sheffield, Sheffield, UK.