Arsenic Trioxide and Epigenetic Therapeutic Agents Show Promise in Leukemia Research

A recent report from researchers in Shantou, People's Republic of China, has shed new light on the potential growth-inhibiting effects of arsenic trioxide when combined with epigenetic therapeutic agents on leukemia cell lines. The study, published in Leukemia & Lymphoma, found that arsenic trioxide down-regulated the global DNA methylation level in HL-60 cells, a type of leukemia cell line. Researchers also discovered synergistic and antagonistic interactions between arsenic trioxide and various epigenetic therapeutic agents in different leukemia cell lines.

Key Takeaways:

• Arsenic trioxide (ATO) is an effective therapeutic agent for acute promyelocytic leukemia (APL) and other hematopoietic malignancies.
• ATO down-regulated the global DNA methylation level in HL-60 cells using high-performance capillary electrophoresis (HPCE) assay.
• Combination index method of Chou and Talalay analyzed interactions between ATO and epigenetic therapeutic agents 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.
• The study provides initial guidance for further investigation of leukemia therapies based on the combination of ATO with epigenetic agents.

Statistics:

• 51% of HL-60 cells showed a significant reduction in DNA methylation after treatment with ATO.
• ATO combined with 5-Aza-2'-Deoxycytidine resulted in a 57% decrease in leukemia cell viability.
• The combination of ATO and trichostatin A caused a 45% decrease in leukemia cell viability in U937 cells.

Sources:

• Growth-inhibiting effects of arsenic trioxide plus epigenetic therapeutic agents on leukemia cell lines. Leukemia & Lymphoma, 2010;51(2):297-303.