title: The inhibition of lactate dehydrogenase A hinders the transcription of histone 2B gene independently from the block of aerobic glycolysis.
abstract: Most cancer cells use aerobic glycolysis to fuel their growth and many efforts are made to selectively block this metabolic pathway in cancer cells by inhibiting lactate dehydrogenase A (LDHA). However, LDHA is a moonlighting protein which exerts functions also in the nucleus as a factor associated to transcriptional complexes. Here we found that two small molecules which inhibit the enzymatic activity of LDHA hinder the transcription of histone 2B gene independently from the block of aerobic glycolysis. Moreover, we observed that silencing this gene reduces cell replication, hence suggesting that the inhibition of LDHA can also affect the proliferation of normal non-glycolysing dividing cells.
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Brighenti
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy.
authors.forename: Domenica
authors.initials: D
authors.lastname: Carnicelli
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy. Electronic address: maurizio.brigotti@unibo.it.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Brigotti
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Fiume
mesh_terms: D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D005690:Galactose / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology; D006019:Glycolysis / Q000187:drug effects / Q000235:genetics*; D045325:HCT116 Cells; D006657:Histones / Q000235:genetics*; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D000080864:Lactate Dehydrogenase 5; D010072:Oxamic Acid / Q000494:pharmacology; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D054852:Small Molecule Libraries / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects / Q000235:genetics*
chemical_list: D006657:Histones; D007527:Isoenzymes; D054852:Small Molecule Libraries; D007770:L-Lactate Dehydrogenase; D000080864:Lactate Dehydrogenase 5; D005947:Glucose; D010072:Oxamic Acid; D005690:Galactose
keywords: Anti-proliferative agents; GSK 2837808A; Histone 2B gene transcription inhibitors; Nuclear LDHA inhibition; Oxamic acid