Involvement of reactive oxygen species in 2-methoxyestradiol-induced apoptosis in human neuroblastoma cells

Neuroblastoma is the most common extra-cranial solid tumor in children. Despite advances in the treatment of childhood cancer, outcomes for children with advanced-stage neuroblastoma remain poor. Here we reported that 2-methoxyestradiol (2-ME) inhibited the proliferation and induced apoptosis in human neuroblastoma SK-N-SH and SH-SY5Y cells. 2-ME treatment also resulted in the generation of ROS and the loss of mitochondrial membrane potential in SK-N-SH and SH-SY5Y, indicating that 2-ME-induced apoptosis is mediated by ROS. This is supported by the results that have shown that co-treatment with antioxidants, VC, L-GSH and MitoQ10, decreased 2-ME-induced generation of ROS and the loss of the mitochondrial membrane potential, increased the Bcl-2/Bax ratio, decreased 2-ME-induced activation of caspase-9 and caspase-3 and the up-regulation of apoptosis-inducing factor (AIF), and prevented 2-ME-induced apoptosis in SK-N-SH and SH-SY5Y cells. These results suggested that oxidative stress plays an important role in 2-ME-induced apoptotic death of human neuroblastoma cells.