Growth-inhibiting effects of arsenic trioxide plus epigenetic therapeutic agents on leukemia cell lines.
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.
Peng
Chun-Yan
CY
Department of Biochemistry, School of Medicine, Shantou University, Shantou, Guangdong, China.
Jiang
Jikai
J
Zheng
Hai-Tao
HT
Liu
Xiao-Shan
XS
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*
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