Voltage-sensitive ion channels and cancer

Fiske, Jamie L.; Fomin, Victor P.; Brown, Milton L.; Duncan, Randall L.; Sikes, Robert A.

doi:10.1007/s10555-006-9017-z

Cited by 126 publications

(106 citation statements)

References 49 publications

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“…of all K + channels, most studies are devoted to the impact of voltage-gated K + channels on proliferation and apoptosis of tumor cells (6,25). gliomas are the most common malignant brain tumors (26), the levels of expression of Kv1.5 and 1.3 channel subtypes discriminated between various glioma groups, and a clear differential expression of Kv1.5 was observed according to malignancy grade (27).…”

Section: Discussionmentioning

confidence: 99%

“…accumulating evidence has proved that a variety of K + channels, including voltage-gated (2), calcium-activated (3), two-pore domain (4) and inward rectifier (5) K + channels are overexpressed in tumorous tissues compared to their healthy counterparts. they control the membrane potential as well as electrical signaling and are known to be involved in the regulation of proliferation, cell cycle progression and apoptosis of tumor cells (6).…”

Section: Introductionmentioning

confidence: 99%

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

Xiang

et al. 2014

International Journal of Oncology

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Xiang

et al. 2014

International Journal of Oncology

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“…For instance, the complex interplays of ionic channels in neuronal, muscle, and pancreatic cells shape their action potential profiles and, subsequently, physiological functions from cognition to heart pumping and insulin secretion. As for inexcitable cells, several K ϩ channels have been implicated in the proliferation, cell cycle transition, and apoptosis of mesenchymal stem cells (MSCs) and tumor cells (3,5,6,9,10,19,20). Previously, we reported (24) that several specialized ion channels are functionally expressed in hESCs.…”

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confidence: 99%

Electrophysiological properties of human induced pluripotent stem cells

Jiang

Rushing

Kong

et al. 2010

American Journal of Physiology-Cell Physiology

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Human embryonic stem cells (hESCs) can self-renew while maintaining their pluripotency. Direct reprogramming of adult somatic cells to induced pluripotent stem cells (iPSCs) has been reported. Although hESCs and human iPSCs have been shown to share a number of similarities, such basic properties as the electrophysiology of iPSCs have not been explored. Previously, we reported that several specialized ion channels are functionally expressed in hESCs. Using transcriptomic analyses as a guide, we observed tetraethylammonium (TEA)-sensitive (IC50 = 3.3 ± 2.7 mM) delayed rectifier K+ currents ( IKDR) in 105 of 110 single iPSCs (15.4 ± 0.9 pF). IKDR in iPSCs displayed a current density of 7.6 ± 3.8 pA/pF at +40 mV. The voltage for 50% activation ( V1/2) was −7.9 ± 2.0 mV, slope factor k = 9.1 ± 1.5. However, Ca2+-activated K+ current ( IKCa), hyperpolarization-activated pacemaker current ( If), and voltage-gated sodium channel (NaV) and voltage-gated calcium channel (CaV) currents could not be measured. TEA inhibited iPSC proliferation (EC50 = 7.8 ± 1.2 mM) and viability (EC50 = 5.5 ± 1.0 mM). By contrast, 4-aminopyridine (4-AP) inhibited viability (EC50 = 4.5 ± 0.5 mM) but had less effect on proliferation (EC50 = 0.9 ± 0.5 mM). Cell cycle analysis further revealed that K+ channel blockers inhibited proliferation primarily by arresting the mitotic phase. TEA and 4-AP had no effect on iPSC differentiation as gauged by ability to form embryoid bodies and expression of germ layer markers after induction of differentiation. Neither iberiotoxin nor apamin had any function effects, consistent with the lack of IKCa in iPSCs. Our results reveal further differences and similarities between human iPSCs and hESCs. A better understanding of the basic biology of iPSCs may facilitate their ultimate clinical application.

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“…With the development of patch clamp technique and molecular biology, recent studies have revealed that ion channels were associated with different aspects of carcinogenic process by involving in cell proliferation, multidrug resistance, migration and invasion (3,4). The functional expression levels of potassium, calcium and chloride channels had been widely investigated over the past few decades, but little is known about the sodium channels in ovarian cancer (5,6).…”

Section: Introductionmentioning

confidence: 99%

Expression of voltage-gated sodium channel α subunit in human ovarian cancer

Gao

Shen²,

Cai³

et al. 2010

Oncol Rep

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Abstract. Voltage-gated sodium channels (VGSC) play important roles in the development and progression of many cancers. We report the possible roles of VGSC in human ovarian cancer. Relative mRNA expression levels of Nav1.1, Nav1.3, Nav1.4 and Nav1.5, analyzed by RT-PCR, were significantly higher in ovarian cancers cells compared with normal ovarian tissues; relative mRNA expression levels of Nav1.2, Nav1.4, Nav1.5 and Nav1.7 were significantly increased in highly metastatic ovarian cancer cells (Caov-3 and SKOV-3) compared with low-metastatic ovarian cancer cells (Anglne). Treatment of 30 μM tetrodotoxin reduced by 50-60% migration and invasion of Caov-3 and SKOV-3 without affecting proliferation. Real-time PCR, Western blot analysis and immunohistochemistry assays revealed that functional expression levels of Nav1.5 might be correlated with the grade and metastasis of ovarian cancer. Our findings suggested that abnormal expression of Nav1.5 could be an integral component of the metastatic process in human ovarian cancer and might serve as a therapeutic target in ovarian cancer treatment. IntroductionOvarian cancer is the most fatal cancer in women in the world. The overwhelming majority of patients are found at advanced disease stage because of no obvious symptoms. Therefore, it is necessary to find effective diagnosis and therapy methods (1).Ion channels are functionally expressed in almost all tissues and cell types as the main signaling molecules (2). With the development of patch clamp technique and molecular biology, recent studies have revealed that ion channels were associated with different aspects of carcinogenic process by involving in cell proliferation, multidrug resistance, migration and invasion (3,4). The functional expression levels of potassium, calcium and chloride channels had been widely investigated over the past few decades, but little is known about the sodium channels in ovarian cancer (5,6).Voltage-gated sodium channel (VGSC) mediates an inward sodium current during the initial phase of potential action in excitable cells, composed of principal · subunit (VGSC·) and auxiliary ß subunits (VGSCß) (7). A window of voltage has been found at cancer cellular normal membrane potential, where there is a continuous entry of sodium because of the partial opening of VGSC·, the entry sodium might be responsible for the disrupting intracellular ion homeostasis (6,8). Therefore, it is important to investigate the roles of VGSC· in carcinogenic process. The functional subunits of VGSC· are the Nav1 family (Nav1.1-1.9), each member of the Nav1 family consists of 4 homologous domains (D1-D4) and every domain has 6 transmembrane segments (S1-S6) (9). Tetrodotoxin (TTX) is the specific blocker of VGSC, according to the sensitivity to TTX, VGSC is described TTX-sensitive (TTX-S; Nav1.1-1.4, Nav1.6-1.7) and TTX-resistant (TTX-R; Nav1.5, Nav1.8-1.9) (10). Among the family, Nav1.5 and Nav1.7 have been found to potentiate metastasis of many cancers (11-13).The aim of this study was to investigate the function...

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Voltage-sensitive ion channels and cancer

Cited by 126 publications

References 49 publications

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

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

Electrophysiological properties of human induced pluripotent stem cells

Expression of voltage-gated sodium channel α subunit in human ovarian cancer

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