Background: Arsenic trioxide (As2O3) has been identified as an effective drug for the treatment of acute promyelocytic leukemia (APL). However, the role of As2O3 during the erythroid differentiation of human leukemic cells remains unknown. In this study, we investigated the in vitro effects of As2O3 on the erythroid differentiation of the K562 cell line and also on the expression and regulation of the apoptotic modulators of this process.
Methods: The K562 cells were cultured in the presence of 0.1, 0.5 and 1.0ՌM As2O3, or they were cultured in the presence of 1.0 and 10ՌM all trans retinoic acid (ATRA). The expression of glycophorin A before and after treatment with As2O3 or with ATRA in the K562 cells was assessed by flow cytometry and western blotting. The expressions of Bcl-2 and caspase-3 were determined by western blotting.
Results: The viability of the K562 cells was not decreased after treating with 0.1 and 0.5ՌM of As2O3, but the viability was significantly reduced at a dose of 1.0ՌM. Caspase 3 activation was not observed at 0.1 and 0.5ՌM of As2O3 until 12 days, but Caspase 3 was activated by 1.0ՌM of As2O3 from day 3. The expression of glycophorin A was increased in dose dependent manner by As2O3 treatment, but this was not changed in the ATRA treated K562 cells. The expression of Bcl-2 was increased by 0.1 and 0.5ՌM of As2O3, but it was abruptly reduced by 1.0ՌM of As2O3.
Conclusion: These results suggest that As2O3 induces the erythroid differentiation of K562 cells and that 1.0ՌM of As2O3 induces apoptosis through the down-regulation of Bcl-2.

Keywords: Arsenic trioxide, Differentiation, Apoptosis, ATRA, K562