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Regulation Of Migration and Proliferation of Glioma Cells by Modulating the Ion Channel Activity.
Author(s) -
Rooj Arun Kumar,
Fuller Catherine M,
Benos Dale J
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.608.7
Subject(s) - glioma , cell migration , chemistry , cell cycle , amiloride , microbiology and biotechnology , downregulation and upregulation , cell growth , in vitro , ion channel , cell , biophysics , biochemistry , cancer research , biology , sodium , receptor , organic chemistry , gene
The movement of cations through ion channels is essential for the migration of glioma cells. We have previously reported that malignant glioma cells express an amiloride sensitive cation conductance that is not detected in normal astrocytes. In the present study, we investigate the potential role of this ion channel to regulate the migration and cell cycle processes of glioma cells. We found that the blocking of Acid Sensitive Ion Channel 1 by Psalmotoxin‐1 (40 amino acid synthetic peptide) significantly inhibited both migration and proliferation of D54MG and U251 glioma cells, using in vitro transwell migration and in‐vitro scratch wound assays. We also found that both PcTx‐1 and benzamil caused a significant cell cycle arrest of D54MG cells in G0/G1 (by 18% and 19%, respectively), and reduced accumulation in the S phase (by 61% and 49%, respectively), and G2/M phase (by 51% and 32%, respectively) (n=3–4; P <0.01) at 24h of incubation. PcTX‐1 and benzamil showed the same effect after 48h of incubation time. An unfolded control peptide had no significant effect compared to PcTX‐1. PcTX‐1 also induced upregulation of cyclin dependent kinase inhibitor (CDKI) proteins (p21 Cip1 and p27 Kip1 ) in D54MG cells. Thus, our data implicate the potential role of this cation conductance in migration and in progression of the cell cycle in glioma cells. This study was supported by NIH grants CA101952 and DK037206.