Sammanfattning

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.

Nyckelord

Mast cells; mastocytosis; histones; demethylase; caspases

Publicerad i

Anticancer Research
2020, Volym: 40, nummer: 5, sidor: 2525-2536 Utgivare: INT INST ANTICANCER RESEARCH

SLU författare

• Pejler, Gunnar

  • Institutionen för husdjurens biovetenskaper, Sveriges lantbruksuniversitet
    
  • Uppsala universitet

UKÄ forskningsämne

Cell- och molekylärbiologi


Publikationens identifierare

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

Permanent länk till denna sida (URI)

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