Molecular and Cellular Biochemistry

, Volume 398, Issue 1–2, pp 95–104 | Cite as

Ouabain elicits human glioblastoma cells apoptosis by generating reactive oxygen species in ERK-p66SHC-dependent pathway



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.


Glioblastoma Ouabain ROS p66Shc Na+/K+-ATPase 



The project was supported by the Fundamental Research Funds for the Central Universities (No.XJTU-HRT-002) and supported by the National Natural Science Foundation of China (No. 81200545).


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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Xiaofei Yan
    • 1
    • 2
  • FenLi Liang
    • 3
  • Dongmin Li
    • 1
  • Jin Zheng
    • 2
  1. 1.Department of Biochemistry and Molecular Biology, Medical SchoolXi’an Jiaotong UniversityXi’anPeople’s Republic of China
  2. 2.First Affiliated Hospital of Medical College of Xi’an Jiaotong UniversityXi’anPeople’s Republic of China
  3. 3.Center for Cancer Research, Medical SchoolXi’an Jiaotong UniversityXi’anPeople’s Republic of China

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