Combination Effect of Deferoxamine and Arsenic Trioxide on Viability and Vitality of APL Like Cell Line.

Abstract

Background: Arsenic trioxide is an activist agent in the treatment of acute promyelocytic leukemia (APL), which acts alone, but has an adverse effect on patients. Moreover, deferoxamine has antiproliferative activity and induces leukopenia. In order to enhance antileukemic effectiveness and to reduce the dosage of arsenic trioxide, the combination effect of it with deferoxamine (DFO) was evaluated on the APL cell line (NB4).

Methods: In this experimental study, to investigate the cytotoxic effects of ATO/DFO in acute promyelocytic leukemia, the NB4 cell line (provided by Pasteur Institute of Iran) was treated with different doses and then at 24, 48, and 72 hrs intervals, the percentage of survival, cell count, metabolic activity and apoptosis induction were investigated respectively. Also, hTERT gene expression was analyzed by the RT-PCR method.

Results: We found that DFO alone and in combination with ATO has cytotoxic and antiproliferative effects, and reduces viability and cell metabolic activity in the NB4 cell line in a dose and time-dependent manner. In addition, this combination causes an increase in apoptosis, up-regulation of Caspase-3, and down-regulation of hTERT genes in cells.

Conclusion: Combined ATO/ DFO treatment cooperatively decreased the mRNA levels of the hTERT and increased the mRNA levels of Caspase-3 in a time-dependent manner compared to DFO alone.