title: Combined treatment with low concentrations of decitabine and SAHA causes cell death in leukemic cell lines but not in normal peripheral blood lymphocytes.
abstract: Epigenetic therapy reverting aberrant acetylation or methylation offers the possibility to target preferentially tumor cells and to preserve normal cells. Combination epigenetic therapy may further improve the effect of individual drugs. We investigated combined action of demethylating agent decitabine and histone deacetylase inhibitor SAHA (Vorinostat) on different leukemic cell lines in comparison with peripheral blood lymphocytes. Large decrease of viability, as well as huge p21WAF1 induction, reactive oxygen species formation, and apoptotic features due to combined decitabine and SAHA action were detected in leukemic cell lines irrespective of their p53 status, while essentially no effect was observed in response to the combined drug action in normal peripheral blood lymphocytes of healthy donors. p53-dependent apoptotic pathway was demonstrated to participate in the wtp53 CML-T1 leukemic cell line response, while significant influence of reactive oxygen species on viability decrease has been detected in p53-null HL-60 cell line.
authors.affiliation: Institute of Hematology and Blood Transfusion, Prague, Czech Republic. brodska@uhkt.cz
authors.forename: Barbora
authors.initials: B
authors.lastname: Brodská
authors.forename: Aleš
authors.initials: A
authors.lastname: Holoubek
authors.forename: Petra
authors.initials: P
authors.lastname: Otevřelová
authors.forename: Kateřina
authors.initials: K
authors.lastname: Kuželová
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects*; D001374:Azacitidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D002478:Cells, Cultured; D000077209:Decitabine; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006877:Hydroxamic Acids / Q000008:administration & dosage*; D007938:Leukemia / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D000077337:Vorinostat
chemical_list: D000964:Antimetabolites, Antineoplastic; D006877:Hydroxamic Acids; D000077337:Vorinostat; D000077209:Decitabine; D001374:Azacitidine