title: Involvement of reactive oxygen species in 2-methoxyestradiol-induced apoptosis in human neuroblastoma cells.
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.
authors: School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, Henan, China.
authors: Qi
authors: Q
authors: Zhang
authors: Yan
authors: Y
authors: Ma
authors: Yue-Fang
authors: YF
authors: Cheng
authors: Wen-Jie
authors: WJ
authors: Li
authors: Zhenzhong
authors: Z
authors: Zhang
authors: Shao-Yu
authors: SY
authors: Chen
mesh_terms: D000077584:2-Methoxyestradiol; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D051033:Apoptosis Inducing Factor / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D004789:Enzyme Activation / Q000187:drug effects; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D009447:Neuroblastoma / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D009943:Organophosphorus Compounds / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014451:Ubiquinone / Q000031:analogs & derivatives / Q000494:pharmacology; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000975:Antioxidants; D051033:Apoptosis Inducing Factor; C494826:BAX protein, human; D009943:Organophosphorus Compounds; D017382:Reactive Oxygen Species; D051028:bcl-2-Associated X Protein; D014451:Ubiquinone; C429014:mitoquinone; D004958:Estradiol; D000077584:2-Methoxyestradiol; D053148:Caspase 3; D053453:Caspase 9