1. Involvement of reactive oxygen species in 2-methoxyestradiol-induced apoptosis in human neuroblastoma cells.
- Author
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Zhang Q, Ma Y, Cheng YF, Li WJ, Zhang Z, and Chen SY
- Subjects
- 2-Methoxyestradiol, Antioxidants pharmacology, Apoptosis drug effects, Apoptosis Inducing Factor metabolism, Caspase 3 metabolism, Caspase 9 metabolism, Cell Line, Tumor, Cell Proliferation drug effects, Drug Screening Assays, Antitumor, Enzyme Activation drug effects, Estradiol pharmacology, Humans, Membrane Potential, Mitochondrial drug effects, Neuroblastoma pathology, Organophosphorus Compounds pharmacology, Ubiquinone analogs & derivatives, Ubiquinone pharmacology, bcl-2-Associated X Protein metabolism, Estradiol analogs & derivatives, Neuroblastoma drug therapy, Neuroblastoma metabolism, Reactive Oxygen Species metabolism
- Abstract
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 MitoQ(10), 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., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)
- Published
- 2011
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