title: Ouabain elicits human glioblastoma cells apoptosis by generating reactive oxygen species in ERK-p66SHC-dependent pathway.
abstract: Excessive reactive oxygen species (ROS) generation has been implicated as one of main agents in ouabain-induced anticancer effect. Unfortunately, the signaling pathways under it are not very clarified. In the present study, we investigated the molecular mechanism involved in ouabain-induced ROS generation and cell apoptosis on human U373MG and U87MG glioma cells. Ouabain-induced glioblastoma cells apoptosis and increased ROS generation. Clearance ROS by three different ROS scavenger partly, but not totally, reversed ouabain's effect on cell apoptosis. Ouabain-induced ROS generation was not regulated by calcium overload, reduced nicotinamide adenine dinucleotide phosphate oxidation, but by p66Shc phosphorylation. Ouabain treatment increased p66Shc Ser36 phosphorylation. Knockdown of p66Shc by siRNA significantly inhibited ROS generations in response to ouabain. Ouabain-induced p66Shc phosphorylation through Src/Ras/extracellular signal-regulated kinase signal pathway. Our results uncovered a novel signaling pathway with p66Shc, ouabain-induced ROS generation, and glioblastoma cell apoptosis.
authors.affiliation: Department of Biochemistry and Molecular Biology, Medical School, Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, People's Republic of China, 279057894@qq.com.
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Yan
authors.forename: FenLi
authors.initials: F
authors.lastname: Liang
authors.forename: Dongmin
authors.initials: D
authors.lastname: Li
authors.forename: Jin
authors.initials: J
authors.lastname: Zheng
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005909:Glioblastoma / Q000378:metabolism / Q000473:pathology; D006801:Humans; D010042:Ouabain / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D034622:RNA Interference; D017382:Reactive Oxygen Species / Q000378:metabolism*; D055765:Shc Signaling Adaptor Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D013997:Time Factors; D018631:ras Proteins / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; C528024:SHC1 protein, human; D055765:Shc Signaling Adaptor Proteins; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D010042:Ouabain; D019061:src-Family Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D053148:Caspase 3; D018631:ras Proteins; D002118:Calcium