The Histone Deacetylase Inhibitor BML-210 Influences Gene and Protein Expression in Human Promyelocytic Leukemia NB4 Cells via Epigenetic Reprogramming.
Today, cancer is understood as an epigenetic as well as genetic disease. The main epigenetic hallmarks of the cancer cell are DNA methylation and histone modifications. Proteins such as histone deacetylases (HDACs) that cause modifications of histones and other proteins can be targets for novel anticancer agents. Recently, interest in compounds that can inhibit HDACs increased, and now there are many HDACs inhibitors (HDACIs) available with different chemical structures, biological and biochemical properties; hopefully some of them will succeed, probably in combination with other agents, in cancer therapies. In our study we focused on the novel HDACI-BML-210. We found that BML-210 (N-phenyl-N'-(2-Aminophenyl)hexamethylenediamide) inhibits the growth of NB4 cells in dose- and time-dependent manner. In this study we also examined how expression and activity of HDACs are affected after leukemia cell treatment with BML-210. Using a mass spectrometry method we identified proteins that changed expression after treatment with BML-210. We prepared RT-PCR analysis of these genes and the results correlated with proteomic data. Based on these and other findings from our group, we suggest that HDACIs, like BML-210, can be promising anticancer agents in promyelocytic leukemia treatment.
Department of Molecular Cell Biology, Institute of Biochemistry, Vilnius University, Mokslininkų 12, Vilnius LT 08662, Lithuania. veronika.borutinskaite@bchi.vu.lt.
Veronika
V
Borutinskaitė
Department of Molecular Cell Biology, Institute of Biochemistry, Vilnius University, Mokslininkų 12, Vilnius LT 08662, Lithuania. ruta.navakauskiene@bchi.vu.lt.
Rūta
R
Navakauskienė
D000813:Anilides / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015415:Biomarkers; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D044127:Epigenesis, Genetic / Q000187:drug effects*; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects*; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics* / Q000378:metabolism; D020543:Proteome; D040901:Proteomics / Q000379:methods
D000813:Anilides; D015415:Biomarkers; D056572:Histone Deacetylase Inhibitors; C514580:N1-(2-aminophenyl)-N8-phenyloctanediamide; D020543:Proteome; D006655:Histone Deacetylases
ATRA; BML-210; HDAC; granulocytic differentiation; leukemia