Voltage-gated K+ channel blocker quinidine inhibits proliferation and induces apoptosis by regulating expression of microRNAs in human glioma U87-MG cells

Abstract

Abstract. accumulating evidence has proved that potassium channels (K + channels) are involved in regulating cell proliferation, cell cycle progression and apoptosis of tumor cells. However, the precise cellular mechanisms are still unknown. in the present study, we investigated the effect and mechanisms of quinidine, a commonly used voltage-gated K + channel blocker, on cell proliferation and apoptosis of human glioma U87-MG cells. We found that quinidine significantly inhibited the proliferation of u87-Mg cells and induced apoptosis in a dose-dependent manner. the results of caspase colorimetric assay showed that the mitochondrial pathway was the main mode involved in the quinidine-induced apoptotic process. furthermore, the concentration range of quinidine, which inhibited voltage-gated K + channel currents in electrophysiological assay, was consistent with that of quinidine inhibiting cell proliferation and inducing cell apoptosis. in u87-Mg cells treated with quinidine (100 µmol/l), 11 of 2,042 human micrornas (mirnas) were upregulated and 16 were downregulated as detected with the mirna array analysis. the upregulation of mir-149-3p and downregulation of mir-424-5p by quinidine treatment were further verified by using quantitative real-time PCR. In addition, using mirna target prediction program, putative target genes related to cell prolif eration and apoptosis for two differentially expressed mirnas were predicted. taken together, these data suggested that the anti-proliferative and pro-apoptosis effect of voltage-gated K + channel blocker quinidine in human glioma cells was mediated at least partly through regulating expression of mirnas, and provided further support for the mechanisms of voltage-gated K + channels in mediating cell proliferation and apoptosis.

Akinesia and freezing caused by Na+ leak‐current channel (NALCN) deficiency corrected by pharmacological inhibition of K+ channels and gap junctions

“… Mancilla and Rojas, ; 2 Wu, ; 3 Edwards and Weston, ; 4 Rogawski and Barker, ; 5 Caballero et al, ; 6 Mergenthaler et al, ; 7 Ru et al, ; 8 Levite et al, ; 9 Hille, ; 10 Bruner et al, ; 11 Päsler et al, ; 12 Zünkler, ; 13 Duan et al, ; 14 Li et al, ; 15 Liu et al, ; 16 Tarr et al, .…”

miR-149 in Human Cancer: A Systemic Review

“…Furthermore, miR-149-3p was found upregulated in U87-MG cells following treatment of quinidine, a voltage-gated K + channel blocker, leading to proliferation inhibition and apoptosis induction of glioma cells. 22 …”

“… 64 Proliferation inhibition and apoptosis induction were observed using expression enhancement of miR-149-3p in glioma cells. 22 Moreover, among various cancers, metastasis was repressed using transfecting miR-149-5p mimics in vitro and in vivo . [29, 35, 36] And chemoresistance to 5-Fluorouracil was suppressed by introducing miR-149-5p mimics in colorectal cancer cells.…”

Inhibition of voltage‑gated potassium channels affect expressions of miR-126 and miR-126* in breast cancer cell lines

“…Some microRNAs have been seen to play a role in the formation of cancer and development mechanism. Quinidine is known to have anti-proliferative and pro-apoptotic effects, and Ru et al demonstrated that voltage-gated potassium channel blocker quinidine regulates some miRNAs expression (42). Meng et al (2012) previously reported that IC50 values were reduced in cells treated with miR-155 inhibitor together with taxol compared to a control group treated with taxol alone.…”