NMR spectroscopic investigation of the effects of LDH inhibitor on glucose metabolism in cancer cells

Sodium oxamate is an inhibitor of lactate dehydrogenase (LDH), specifically LDH-A, an important enzyme that is active in cell and is responsible for catalyzing the reversible conversion of pyruvate to lactate. In this work, we have investigated via carbon-13 nuclear magnetic resonance (NMR) spectroscopy the metabolic effect of varying concentration of sodium oxamate and the role of glutamine on [1-13C] glucose metabolism in a variety of cultured cancers cell including renal cell carcinoma (786-O), hepatocellular carcinoma (HepG-2), and glioblastoma (SfXL cells). Our results reveal that highest concentration of sodium oxamate affect lactate production and other glucose metabolites in these cancer cell. Intra- and extra-cellular metabolic products of glucose will be discussed in light of the key role of glutamine in glucose metabolism. This study is supported by the Welch Foundation grant AT‐2111‐20220331, US Department of Defense CDMRP grants W81XWH-21-1-0176, W81XWH-22-1-0105, W81XWH-19-1-0741, and W81XWH-22-1-0003.