title: Methylseleninic acid inhibits HDAC activity in diffuse large B-cell lymphoma cell lines.
abstract: OBJECTIVE
  Selenium is a trace element that is fundamental to human health. Research has mainly focussed on its role in cancer prevention, but recent evidence supports its role in established cancer, with high concentrations inducing tumour cell death and non-toxic concentrations sensitising cells to chemotherapy. However, the precise mechanism of selenium action is not clear. The effect of methylseleninic acid (MSA), an organic selenium compound, on histone deacetylase (HDAC) activity in diffuse large B-cell lymphoma cell lines is reported here.
  
  
  METHODS
  Lymphoma cell lines were exposed to MSA under normoxic and hypoxic conditions. Protein expression was determined by western blotting, HDAC activity and VEGF concentration by fluorimetric and electrochemiluminescence assays, respectively, and intracellular selenium metabolites quantified by mass spectrometry.
  
  
  RESULTS
  MSA inhibited HDAC activity, which resulted in the acetylation of histone H3 and α-tubulin. However, cellular metabolism of MSA to methylselenol was required for this effect. Dimethylselenide, the methylation product of methylselenol, was found to be the major intracellular metabolite. MSA also inhibited HIF-1α expression and VEGF secretion, a possible consequence of HDAC inhibition.
  
  
  CONCLUSIONS
  The ability of methylselenol to inhibit HDAC activity has not been previously reported, thus providing a novel mechanism of selenium action.
authors.affiliation: Centre for Haemato-Oncology, Barts Cancer Institute, Queen Mary University of London, London, UK. s.a.kassam@qmul.ac.uk
authors.forename: Shireen
authors.initials: S
authors.lastname: Kassam
authors.forename: Heidi
authors.initials: H
authors.lastname: Goenaga-Infante
authors.forename: Lenushka
authors.initials: L
authors.lastname: Maharaj
authors.forename: Crispin T
authors.initials: CT
authors.lastname: Hiley
authors.forename: Simone
authors.initials: S
authors.lastname: Juliger
authors.forename: Simon P
authors.initials: SP
authors.lastname: Joel
mesh_terms: D015153:Blotting, Western; D045744:Cell Line, Tumor; D003553:Cystine / Q000187:drug effects / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000037:antagonists & inhibitors; D016393:Lymphoma, B-Cell / Q000201:enzymology*; D016566:Organoselenium Compounds / Q000494:pharmacology*; D012643:Selenium / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: C497442:HIF1A protein, human; D056572:Histone Deacetylase Inhibitors; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D016566:Organoselenium Compounds; D042461:Vascular Endothelial Growth Factor A; D003553:Cystine; C008493:methylselenic acid; D006655:Histone Deacetylases; D012643:Selenium