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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4 Citations (Scopus)


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
Pages (from-to)1375-1385
Number of pages11
JournalNucleosides, Nucleotides and Nucleic Acids
Issue number12
Early online date2022
Publication statusPublished - 2022


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

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