The effect of lactate dehydrogenase-A inhibition on intracellular nucleotides and mitochondrial respiration in pancreatic cancer cells

Marika Franczak, Barbara Kutryb-Zajac, Btissame el Hassouni, Elisa Giovannetti, Carlotta Granchi, Filippo Minutolo, Ryszard T. Smolenski, Godefridus J. Peters

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Pancreatic cancer (PC) is one of the most lethal malignancies. PC is characterized by a high expression of the glucose transporter GLUT-1 and of lactate dehydrogenase A (LDH-A). The novel LDH-A inhibitor NHI-Glc-2 was designed for a better uptake via GLUT-1 and was shown to be cytotoxic against the PC cell line PANC-1. Using RP-HPLC we investigated its effect on adenine nucleotides and NADH/NAD+, while the Seahorse analyzer was used to determine its effect on glycolysis and mitochondrial function. A 24 hour exposure to 10 µM NHI-Glc-2 (around the IC50) decreased the ATP concentration by about 10%, but at 25 µM this decrease was 38%, while NAD+ decreased by 26%, associated with a 35% decrease in the NADH/NAD+ ratio. A 10 µM NHI-Glc-2 decreased extracellular acidification and oxygen consumption (about 75%), as well as the mitochondrial respiration parameters by 50%. In conclusion, LDH-A inhibition markedly affected the energy supply of PANC-1 cells. The respiration data indicated a dependency of the cells on glycolysis and fatty acid oxidation. Supplemental data for this article is available online at
Original languageEnglish
JournalNucleosides, Nucleotides and Nucleic Acids
Early online date2022
Publication statusE-pub ahead of print - 2022


  • Pancreatic cancer
  • glucose transporter 1
  • lactate dehydrogenase A
  • mitochondrial function
  • nucleotides

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