title: Effects of epigenetic-based anti-cancer drugs in leukaemia and multiple myeloma cells.
abstract: Here, we focus on epigenetic changes in leukaemia and MM (multiple myeloma) cells. We show how the histone signature, DNA methylation and levels of select tumour-suppressor proteins can be affected by inhibitors of HDACs (histone deacetylases) and Dnmts (DNA methyltransferases). Both inhibitors, TSA (trichostatin A) and 5-AZA (5-azacytidine), have the ability to change the histone signature in a tumour-specific manner. In MM cells, we observed changes in H3K4 methylation, while in leukaemia cells, H3K9 methylation was especially affected by select inhibitors. Compared with normal peripheral blood lymphocytes, tumour cell samples were characterized by increased H3K9 acetylation, increased H3K4me2, H3K9me2 and HP1α (heterochromatin protein 1α) levels and specific changes were also observed for DNA methylation. Additionally, we showed that the tumour suppressor pRb1 (retinoblastoma protein) is more sensitive to epigenetic-based anti-cancer stimuli than p53. We have found significant decrease in the levels of pRb1 and p53 in both myeloma and leukaemia cells after HDAC inhibition.
authors.affiliation: Institute of Biophysics, Academy of Sciences of the Czech Republic, Brno.
authors.forename: Alžběta
authors.initials: A
authors.lastname: Jugová
authors.forename: Gabriela
authors.initials: G
authors.lastname: Sustáčková
authors.forename: Soňa
authors.initials: S
authors.lastname: Legartová
authors.forename: Lenka
authors.initials: L
authors.lastname: Stixová
authors.forename: Stanislav
authors.initials: S
authors.lastname: Kozubek
authors.forename: Eva
authors.initials: E
authors.lastname: Bártová
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D001374:Azacitidine / Q000494:pharmacology; D000090266:Chromobox Protein Homolog 5; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000235:genetics / Q000378:metabolism; D044127:Epigenesis, Genetic; D020868:Gene Silencing; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006655:Histone Deacetylases / Q000378:metabolism; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D007938:Leukemia / Q000188:drug therapy* / Q000235:genetics; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000235:genetics; D016160:Retinoblastoma Protein / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; C000715594:CBX5 protein, human; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D006877:Hydroxamic Acids; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53; D000090266:Chromobox Protein Homolog 5; C012589:trichostatin A; D015254:DNA Modification Methylases; D006655:Histone Deacetylases; D001374:Azacitidine