Methylseleninic acid inhibits HDAC activity in diffuse large B-cell lymphoma cell lines

  • Shireen Kassam
  • Heidi Goenaga-Infante
  • Lenushka Maharaj
  • Crispin T. Hiley
  • Simone Juliger
  • Simon P. Joel
Short Communication

Abstract

Purpose

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.

Conclusion

The ability of methylselenol to inhibit HDAC activity has not been previously reported, thus providing a novel mechanism of selenium action.

Keywords

Selenium Methylseleninic acid Histone deacetylase HIF1alpha VEGF 

Supplementary material

280_2011_1649_MOESM1_ESM.doc (29 kb)
Supplementary material 1 (DOC 29 kb)

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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Shireen Kassam
    • 1
  • Heidi Goenaga-Infante
    • 2
  • Lenushka Maharaj
    • 1
  • Crispin T. Hiley
    • 3
  • Simone Juliger
    • 1
  • Simon P. Joel
    • 1
  1. 1.Centre for Haemato-Oncology, Barts Cancer InstituteQueen Mary University of LondonLondonUK
  2. 2.LGC LimitedLondonUK
  3. 3.Centre for Molecular Oncology and Imaging, Barts Cancer InstituteLondonUK

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