title: Blockage of potassium channel inhibits proliferation of glioma cells via increasing reactive oxygen species.
abstract: The potassium (K(+)) channel plays an important role in the cell cycle and proliferation of tumor cells, while its role in brain glioma cells and the signaling pathways remains unclear. We used tetraethylammonium (TEA), a nonselective antagonist of big conductance K(+) channels, to block K(+) channels in glioma cells, and antioxidant N-acetyl-l-cysteine (NAC) to inhibit production of intracellular reactive oxygen species (ROS). TEA showed an antiproliferation effect on C6 and U87 glioma cells in a time-dependent manner, which was accompanied by an increased intracellular ROS level. Antioxidant NAC pretreatment reversed TEA-mediated antiproliferation and restored ROS level. TEA treatment also caused significant increases in mRNA and protein levels of tumor-suppressor proteins p53 and p21, and the upregulation was attenuated by pretreatment of NAC. Our results suggest that K(+) channel activity significantly contributes to brain glioma cell proliferation via increasing ROS, and it might be an upstream factor triggering the activation of the p53/p21(Cip1)-dependent signaling pathway, consequently leading to glioma cell cycle arrest.
authors.affiliation: Department of Neurosurgery, the First Affiliated Hospital of Harbin Medical UniversityHarbinChina.
authors.forename: Li
authors.initials: L
authors.lastname: Hu
authors.affiliation: Department of Neurosurgery, the First Affiliated Hospital of Harbin Medical UniversityHarbinChina.
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, the First Affiliated Hospital of Harbin Medical UniversityHarbinChina.
authors.forename: Zhi-Guo
authors.initials: ZG
authors.lastname: Lin
authors.affiliation: Department of Neurosurgery, the First Affiliated Hospital of Harbin Medical UniversityHarbinChina.
authors.forename: Zhi-Chao
authors.initials: ZC
authors.lastname: Jiang
authors.affiliation: Department of Neurosurgery, the First Affiliated Hospital of Harbin Medical UniversityHarbinChina.
authors.forename: Hong-Xing
authors.initials: HX
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, the First Affiliated Hospital of Harbin Medical UniversityHarbinChina.
authors.forename: Shi-Guang
authors.initials: SG
authors.lastname: Zhao
authors.affiliation: Department of Neurosurgery, the First Affiliated Hospital of Harbin Medical UniversityHarbinChina.
authors.forename: Kong-Bin
authors.initials: KB
authors.lastname: Yang
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D015221:Potassium Channels / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D019789:Tetraethylammonium / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D000975:Antioxidants; D050759:Cyclin-Dependent Kinase Inhibitor p21; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; D019789:Tetraethylammonium; D000111:Acetylcysteine