Signal transduction pathways and transcription factors triggered by arsenic trioxide in leukemia cells.

Arsenic trioxide (As(2)O(3)) is widely used to treat acute promyelocytic leukemia (APL). Several lines of evidence have indicated that As(2)O(3) affects signal transduction and transactivation of transcription factors, resulting in the stimulation of apoptosis in leukemia cells, because some transcription factors are reported to associate with the redox condition of the cells, and arsenicals cause oxidative stress. Thus, the disturbance and activation of the cellular signaling pathway and transcription factors due to reactive oxygen species (ROS) generation during arsenic exposure may explain the ability of As(2)O(3) to induce a complete remission in relapsed APL patients. In this report, we review recent findings on ROS generation and alterations in signal transduction and in transactivation of transcription factors during As(2)O(3) exposure in leukemia cells.