Lactate dehydrogenase inhibition affects homologous recombination repair independently of cell metabolic asset; implications for anticancer treatment

• Published in: Biochimica et biophysica acta. General subjects Vol. 1865; no. 1; p. 129760
• Main Authors: Balboni, Andrea, Govoni, Marzia, Rossi, Valentina, Roberti, Marinella, Cavalli, Andrea, Di Stefano, Giuseppina, Manerba, Marcella
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.01.2021
• Subjects: Antineoplastic Agents - pharmacology; assets; Cancer cell metabolism; Cell Line, Tumor; DNA; DNA damage; DNA repair; drug resistance; drugs; energy metabolism; Enzyme Inhibitors - pharmacology; glucose; Glycolysis; Glycolysis - drug effects; Homologous recombination; Humans; L-Lactate Dehydrogenase - antagonists & inhibitors; L-Lactate Dehydrogenase - metabolism; Lactate; Lactate dehydrogenase; neoplasm cells; Neoplasms - drug therapy; Neoplasms - genetics; Neoplasms - metabolism; Olaparib; Phthalazines - pharmacology; Piperazines - pharmacology; Poly(ADP-ribose) Polymerase Inhibitors - pharmacology; Recombinational DNA Repair - drug effects; Glycolysis; Cancer cell metabolism; Lactate dehydrogenase; Olaparib; Lactate; Homologous recombination

Cancer cells show highly increased glucose utilization which, among other cancer-essential functions, was found to facilitate DNA repair. Lactate dehydrogenase (LDH) activity is pivotal for supporting the high glycolytic flux of cancer cells; to our knowledge, a direct contribution of this enzyme in...