Arsenic trioxide induces apoptosis through a reactive oxygen species-dependent pathway and loss of mitochondrial membrane potential in HeLa cells.

Arsenic trioxide (As 2 O 3 ) can induce clinical remission in patients with acute promyelocytic leukemia (APL) through induction of apoptosis. To investigate the potential therapeutic usage of As 2 O 3 in cervical cancer and its possible mechanisms, human cervical cancer cell line HeLa was employed. The cells underwent apoptosis in response to As 2 O 3 , accompanied by a decrease of mitochondrial membrane potential and caspase-3 activation. Overexpression of Bcl-2, however, prevented the dissipation of mitochondrial membrane potential, subsequently protecting the cells from As 2 O 3 -induced apoptosis. As 2 O 3 increased cellular content of reactive oxygen species (ROS), especially hydrogen peroxide (H 2 O 2 ), and the antioxidant N-acetyl-L-cysteine completely suppressed As 2 O 3 -induced apoptosis. Furthermore, incubation of the cells with catalase resulted in significant suppression of As 2 O 3 -induced apoptosis. The above results indicate that the induction of HeLa cell apoptosis by As 2 O 3 involved an early decrease in cellular mitochondrial membrane potential and increase in ROS content, predominantly H 2 O 2 , followed by caspase-3 activation and DNA fragmentation.