Apoptotic effect of arsenic trioxide plus Azidothymidine on APL cell line (NB4) through P21 expression and cell cycle distribution changes

Arsenic trioxide (ATO) is an active drug in treatment of acute promyelocytic leukemia (APL)، but has adverse effects on patients. In order to enhance antileukemic effectiveness and to reduce dosage of ATO، combinatorial effect of it with Azidothymidine (AZT) in apoptosis induction was evaluated on APL cell line (NB4). The cells cultured and treated with 50 μM AZT and/or ATO for 48 hrs and then with apoptosis، cell cycle distribution، and P21 mRNA levels in comparison with untreated cells (control) were analyzed by flow cytometry and Real Time PCR، respectively. ATO led to induction of apoptosis (50. 14% ± 7. 12) in comparison with the control (3. 9% ± 2. 97) through the increment of the cell cycle arrest in G2/M. The apoptotic effect of ATO had been inhibited in cells treated with combination of AZT/ATO (24. 35% ± 4. 65). This inhibition was associated with the relative reduction of the cells in G2/M and relative increase of the cells in G1 phase. While ATO had suppressive effect on p21 gene expression (0. 27±0. 14)، AZT (1. 81 ± 0. 21) and AZT/ATO (2. 06 ± 0. 32) induced it. AZT attenuates ATO-caused apoptosis possibly through the induction of p21 expression and subsequent relative evasion from G2/M arrest and accumulation of cells in G1 phase.