Figure 5.

Schematic representation of the apoptotic mechanisms of arsenic trioxide (ATO) as a therapeutic agent in the treatment of acute promyelocytic leukemia. ATO exerts a dual effect on HL-60 cells by inducing partial differentiation and apoptosis. As shown on Figure 5, the mechanisms by which ATO induces apoptosis is mediated through oxidative stress [13] that leads to DNA damage and cell death [44], up-regulation of p53 tumor suppressor protein and repression of the c-fos transcription factor [18], induction of phosphatidylserine externalization, caspase-3 activation, and nucleosomal DNA fragmentation.