title: Growth-inhibiting effects of arsenic trioxide plus epigenetic therapeutic agents on leukemia cell lines.
abstract: Arsenic trioxide (ATO) is an effective therapeutic agent for acute promyelocytic leukemia (APL) and other hematopoietic malignancies. We found that ATO down-regulated the global DNA methylation level in HL-60 cells with high-performance capillary electrophoresis (HPCE) assay. Using combination index method of Chou and Talalay, interactions between ATO and epigenetic therapeutic agents were analyzed in three human leukemia cell lines (HL-60, U937, and K562). A synergistic interaction was observed in HL-60 cells between ATO and 5-Aza-2'-Deoxycytidine (DAC), while an antagonistic interaction was found in U937 cells between ATO and valproic acid (VPA). The combination of ATO with trichostatin A (TSA) caused an antagonistic interaction in U937 and K562 cells. These results not only highlight possible diversity of the anti-leukemia mechanisms of ATO, but also provide initial guide for further investigation of leukemia therapies based on the combination of ATO with epigenetic agents.
authors.affiliation: Department of Biochemistry, School of Medicine, Shantou University, Shantou, Guangdong, China.
authors.forename: Chun-Yan
authors.initials: CY
authors.lastname: Peng
authors.forename: Jikai
authors.initials: J
authors.lastname: Jiang
authors.forename: Hai-Tao
authors.initials: HT
authors.lastname: Zheng
authors.forename: Xiao-Shan
authors.initials: XS
authors.lastname: Liu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D019175:DNA Methylation / Q000187:drug effects; D015254:DNA Modification Methylases / Q000037:antagonists & inhibitors; D004273:DNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D000077209:Decitabine; D004336:Drug Antagonism; D004357:Drug Synergism; D019075:Electrophoresis, Capillary / Q000379:methods; D006131:Growth Inhibitors / Q000494:pharmacology; D018922:HL-60 Cells; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D020014:K562 Cells; D007938:Leukemia / Q000235:genetics / Q000473:pathology; D010087:Oxides / Q000494:pharmacology*; D020298:U937 Cells; D014635:Valproic Acid / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D001152:Arsenicals; D004273:DNA, Neoplasm; D006131:Growth Inhibitors; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D010087:Oxides; C012589:trichostatin A; D014635:Valproic Acid; D000077209:Decitabine; D015254:DNA Modification Methylases; D001374:Azacitidine; D000077237:Arsenic Trioxide