title: Generation of reactive oxygen species during apoptosis induced by DNA-damaging agents and/or histone deacetylase inhibitors.
abstract: Reactive oxygen species play an important role in the process of apoptosis in many cell types. In this paper, we analyzed the role of ROS in DNA-damaging agents (actinomycin D or decitabine), which induced apoptosis of leukemia cell line CML-T1 and normal peripheral blood lymphocytes (PBL). The possibility of synergism with histone deacetylase inhibitors butyrate or SAHA is also reported. We found that in cancer cell line, ROS production significantly contributed to apoptosis triggering, while in normal lymphocytes treated by cytostatic or cytotoxic drugs, necrosis as well as apoptosis occurred and large heterogeneity of ROS production was measured. Combined treatment with histone deacetylase inhibitor did not potentiate actinomycin D action, whereas combination of decitabine and SAHA brought synergistic ROS generation and apoptotic features in CML cell line. Appropriate decrease of cell viability indicated promising therapeutic potential of this combination in CML, but side effects on normal PBL should be taken into attention.
authors.affiliation: Institute of Hematology and Blood Transfusion, U Nemocnice 1, 12820 Prague 2, Czech Republic. brodska@uhkt.cz
authors.forename: Barbora
authors.initials: B
authors.lastname: Brodská
authors.forename: Aleš
authors.initials: A
authors.lastname: Holoubek
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D002087:Butyrates / Q000494:pharmacology; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D054697:Cytostatic Agents / Q000494:pharmacology; D004249:DNA Damage / Q000187:drug effects; D003609:Dactinomycin / Q000494:pharmacology; D000077209:Decitabine; D004357:Drug Synergism; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D000077337:Vorinostat
chemical_list: D000970:Antineoplastic Agents; D002087:Butyrates; D054697:Cytostatic Agents; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D017382:Reactive Oxygen Species; D003609:Dactinomycin; D000077337:Vorinostat; D000077209:Decitabine; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3; D001374:Azacitidine