Sultan Alanazi1, Fabio Rabelo Melo2, Gunnar Pejler2,3. 1. Uppsala University, Department of Medical Biochemistry and Microbiology, Uppsala, Sweden. 2. Uppsala University, Department of Medical Biochemistry and Microbiology, Uppsala, Sweden Fabio.Melo@imbim.uu.se Gunnar.Pejler@imbim.uu.se. 3. Swedish University of Agricultural Sciences, Department of Anatomy, Physiology and Biochemistry, Uppsala, Sweden.
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. Copyright
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. Copyright