The inhibition of lactate dehydrogenase A hinders the transcription of histone 2B gene independently from the block of aerobic glycolysis

Biochem Biophys Res Commun. 2017 Apr 15;485(4):742-745. doi: 10.1016/j.bbrc.2017.02.119. Epub 2017 Feb 28.

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.

Keywords: Anti-proliferative agents; GSK 2837808A; Histone 2B gene transcription inhibitors; Nuclear LDHA inhibition; Oxamic acid.

MeSH terms

  • Cell Line
  • Cell Proliferation / drug effects
  • Cell Proliferation / genetics
  • Galactose / pharmacology
  • Glucose / pharmacology
  • Glycolysis / drug effects
  • Glycolysis / genetics*
  • HCT116 Cells
  • Histones / genetics*
  • Humans
  • Isoenzymes / antagonists & inhibitors
  • Isoenzymes / genetics
  • Isoenzymes / metabolism
  • L-Lactate Dehydrogenase / antagonists & inhibitors
  • L-Lactate Dehydrogenase / genetics*
  • L-Lactate Dehydrogenase / metabolism
  • Lactate Dehydrogenase 5
  • Oxamic Acid / pharmacology
  • RNA Interference
  • Reverse Transcriptase Polymerase Chain Reaction
  • Small Molecule Libraries / pharmacology
  • Transcription, Genetic / drug effects
  • Transcription, Genetic / genetics*

Substances

  • Histones
  • Isoenzymes
  • Small Molecule Libraries
  • L-Lactate Dehydrogenase
  • Lactate Dehydrogenase 5
  • Glucose
  • Oxamic Acid
  • Galactose