Effects of co-administration of arsenic trioxide and Schiff base oxovanadium complex on the induction of apoptosis in acute promyelocytic leukemia cells

Introduction: Acute promyelocytic leukaemia (APL) is commonly treated with arsenic trioxide (As۲O۳) that has many side effects. Given the increasing trend of studies on beneficial therapeutic properties of synthetic compounds containing vanadium, the present study sought to use Schiff base oxovanadium complex to reduce the needed concentration of arsenic trioxide. Method: The HL-۶۰ cell line, which is a model of APL, was selected and the effects of arsenic trioxide and Schiff base oxovanadium complex were individually and simultaneously evaluated on the cell viability by the MTT assay. Flow cytometry and Real-time RT-PCR were also performed to investigate the rate of apoptosis and the expression of P۵۳ and P۲۱ genes, respectively. Results: The IC۵۰ of arsenic trioxide and Schiff base oxovanadium complex on Hl-۶۰ cells was ۸.۳۷ ± ۰.۳۶ μM and ۳۴.۱۲ ± ۱.۵۲ μg/ml, respectively. At the simultaneous administration of both compounds, the maximum decrease in the cell viability was seen in co-administration of ۴۰ μg/ml of Schiff base oxovanadium complex and ۰.۰۰۱ μM of arsenic trioxide. Real-time RT-PCR indicated that the co-administration of Schiff base oxovanadium complex ۴۰ μg/ml and arsenic trioxide ۰.۰۰۱ μM could increase the expression of P۵۳ and P۲۱ genes by ۳.۷۶ ± ۰.۱۹ and ۶.۵۷ ± ۱.۲۹ fold change, respectively to the control sample. The flow cytometry studies also indicated that this co-administration could induce apoptosis up to ۶۷% ± ۰.۹% significantly higher than the control sample. Conclusion: The use of Schiff base oxovanadium complex could significantly reduce the required dose of arsenic trioxide to induce apoptosis in HL-۶۰ cells.

کلیدواژه ها:

Acute promyelocytic leukemia (APL) ، Arsenic trioxide ، Synthetic vanadium complex ، HL-۶۰