Open AccessBlockage of Potassium Channel Inhibits Proliferation of Glioma Cells Via Increasing Reactive Oxygen Species
Author(s) -
Hu Li,
Lili Li,
Zhiguo Lin,
Zhichao Jiang,
Hongxing Li,
Shen Zhao,
Kongbin Yang
Publication year - 2014
Publication title -
oncology research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 57
eISSN - 1555-3906
pISSN - 0965-0407
DOI - 10.3727/096504014x14098532393518
Subject(s) - reactive oxygen species , glioma , potassium channel , intracellular , cell growth , downregulation and upregulation , antioxidant , chemistry , microbiology and biotechnology , cell cycle , biology , cell , biochemistry , cancer research , endocrinology , gene
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.