title: Potentiation of reactive oxygen species is a marker for synergistic cytotoxicity of MS-275 and 5-azacytidine in leukemic cells.
abstract: Epigenetic modifiers are currently in clinical use for various tumor types. Recently, numerous studies supporting the combination of histone deacetylase inhibitors (HDACi) and DNA methyltransferase inhibitors have emerged, encouraging early clinical trials of these agents together. Here we show that MS-275, an HDACi, and 5-azacytidine, a methyltransferase inhibitor, display synergistic cytotoxicity and apoptosis in AML and ALL cells. Intracellular production of reactive oxygen species (ROS), such as superoxide and hydrogen peroxide, is a novel marker for this synergism in ALL cells. These data suggest that assessment of oxidative stress can serve as a marker of the concerted action of MS-275 and 5-azacytidine.
authors.affiliation: Department of Pediatrics Research, Children's Cancer Hospital at M.D. Anderson Cancer Center, Houston, Texas, United States.
authors.forename: Shan
authors.initials: S
authors.lastname: Gao
authors.forename: Aaron
authors.initials: A
authors.lastname: Mobley
authors.forename: Claudia
authors.initials: C
authors.lastname: Miller
authors.forename: Jessica
authors.initials: J
authors.lastname: Boklan
authors.forename: Joya
authors.initials: J
authors.lastname: Chandra
mesh_terms: D000107:Acetylation; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001374:Azacitidine / Q000494:pharmacology*; D001549:Benzamides / Q000494:pharmacology*; D015415:Biomarkers; D053148:Caspase 3 / Q000502:physiology; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors; D006657:Histones / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D007938:Leukemia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011725:Pyridines / Q000494:pharmacology*; D017382:Reactive Oxygen Species
chemical_list: D000964:Antimetabolites, Antineoplastic; D001549:Benzamides; D015415:Biomarkers; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D011725:Pyridines; D017382:Reactive Oxygen Species; C118739:entinostat; D053148:Caspase 3; D005978:Glutathione; D001374:Azacitidine