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.

Keywords:

• Arsenic trioxide
• epigenetic therapeutic agents
• leukemia
• DNA methylation
• combination index method of Chou and Talalay

Acknowledgments

The authors are grateful to the members in Central Laboratory, School of Medicine, Shantou University for their technical support.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the article.