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

Autor: Marika Franczak, Barbara Kutryb-Zajac, Btissame El Hassouni, Elisa Giovannetti, Carlotta Granchi, Filippo Minutolo, Ryszard T. Smolenski, Godefridus J. Peters
Přispěvatelé: Medical oncology laboratory, CCA - Cancer biology and immunology, Amsterdam Gastroenterology Endocrinology Metabolism
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Franczak, M, Kutryb-Zajac, B, el Hassouni, B, Giovannetti, E, Granchi, C, Minutolo, F, Smolenski, R T & Peters, G J 2022, ' The effect of lactate dehydrogenase-A inhibition on intracellular nucleotides and mitochondrial respiration in pancreatic cancer cells ', Nucleosides, Nucleotides and Nucleic Acids, vol. 41, no. 12, pp. 1375-1385 . https://doi.org/10.1080/15257770.2022.2031215
Nucleosides, Nucleotides and Nucleic Acids, 41(12), 1375-1385. Taylor and Francis Ltd.
ISSN: 1525-7770
DOI: 10.1080/15257770.2022.2031215
Popis: 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 https://doi.org/10.1080/15257770.2022.2031215.
Databáze: OpenAIRE
Externí odkaz: