Histone Methyltransferase Inhibition Has a Cytotoxic Impact on Transformed Mast Cells: Implications for Mastocytosis

Abstract

Background/Aim: Mast cell transformation, as manifested in mastocytosis, can be a serious condition for which there are limited therapeutic options. Mastocytosis cells can be sensitive to histone deacetylase (HDAC) inhibitors, but their sensitivity to other histone-modifying enzymes has not been assessed. Here we addressed this issue. Materials and Methods: Inhibitors of histone methyl transferases, histone demethylases, histone acetyl transferases and HDACs were tested for their effects on growth, viability, caspase-3 activation and annexin V/DRAQ7 staining in transformed mast cells. Results: Transformed mast cells underwent cell death in response to histone methyl transferase and HDAC inhibition, but were not sensitive to histone demethylase or histone acetyl transferase inhibition. Histone methyl transferase inhibition led to cell death with characteristics of apoptosis, as judged by caspase-3 activation. However, DNA fragmentation was not apparent and Annexin V+/DRAQ7(-) cells were not predominant, suggesting a type of cell death differing from classical apoptosis. Conclusion: Histone methyl transferase inhibition could be developed as a novel regimen for targeting mastocytosis.

Keywords

Mast cells; mastocytosis; histones; demethylase; caspases

Published in

Anticancer Research
2020, Volume: 40, number: 5, pages: 2525-2536 Publisher: INT INST ANTICANCER RESEARCH

SLU Authors

• Pejler, Gunnar

  • Department of Animal Biosciences, Swedish University of Agricultural Sciences
    
  • Uppsala University

UKÄ Subject classification

Cell and Molecular Biology


Publication identifier

DOI: https://doi.org/10.21873/anticanres.14223

Permanent link to this page (URI)

https://res.slu.se/id/publ/105764