Potassium channel blockers quinidine and caesium halt cell proliferation in C6 glioma cells via a polyamine-dependent mechanism

Potassium channels are ubiquitous in cells and serve essential functions in physiology and pathophysiology. Potassium channel blockers have been shown to block tumour growth by arresting cells at the G0/G1 checkpoint of the cell cycle. We investigated the effect of quinidine and caesium (Cs+) on cell proliferation, LDH (lactate dehydrogenase) release, free internal calcium, membrane potential, polyamine concentration, ODC (ornithine decarboxylase) activity and polyamine uptake in C6 glioma cells. The EC50 for reducing cell proliferation was 112 μM for quinidine, whereas Cs+ was less effective with an EC50 of 4.75 mM. KCl or sucrose did not affect proliferation. LDH release was augmented by quinidine. Quinidine caused a transient increase in free internal calcium but decreased calcium after a 48 h incubation period. Further 300 μM quinidine depolarized the cell membrane in a similar range as did 30 mM KCl. Quinidine decreased cellular putrescine beyond detection levels while spermidine and spermine remained unaffected. ODC activity was reduced. Addition of putrescine could not override the antiproliferative effect owing to a reduced activity of the polyamine transporter. Our study indicates that the antiproliferative effect of quinidine is not due to a simple membrane depolarization but is caused by a block of ODC activity.

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Effects of chronic application of antidepressants, mood stabilizers, and Ca2+ channel blockers on intracellular Ca2+ mobilization in single C6 glioma cells.

The Japanese Journal of Pharmacology ◽

10.1016/s0021-5198(19)50273-6 ◽

1994 ◽

Vol 64 ◽

pp. 158

Author(s):

Takayuki Yamaji ◽

Ariyuki Kagaya ◽

Yasumasa Okamoto ◽

Teruo Hayashi ◽

Nobutaka Motohashi ◽

...

Keyword(s):

Glioma Cells ◽

C6 Glioma ◽

Mood Stabilizers ◽

C6 Glioma Cells ◽

Channel Blockers

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Volume changes and whole cell membrane currents activated during gradual osmolarity decrease in C6 glioma cells: contribution of two types of K+ channels

AJP Cell Physiology ◽

10.1152/ajpcell.00198.2003 ◽

2004 ◽

Vol 286 (6) ◽

pp. C1399-C1409 ◽

Cited By ~ 20

Author(s):

B. Ordaz ◽

L. Vaca ◽

R. Franco ◽

H. Pasantes-Morales

Keyword(s):

Amino Acid ◽

Glioma Cells ◽

Ionic Currents ◽

C6 Glioma ◽

C6 Glioma Cells ◽

Channel Blockers ◽

Volume Changes ◽

Whole Cell ◽

Outward Currents ◽

Amino Acid Efflux

Volume changes and whole cell ionic currents activated by gradual osmolarity reductions (GOR) of 1.8 mosM/min were characterized in C6 glioma cells. Cells swell less in GOR than after sudden osmolarity reductions (SOR), the extent of swelling being partly Ca2+ dependent. In nominally Ca2+-free conditions, GOR activated predominantly whole cell outward currents. Cells depolarized from the initial −79 mV to a steady state of −54 mV reached at 18% osmolarity reduction [hyposmolarity of −18% (H-18%)]. Recordings of Cl− and K+ currents showed activation at H-3% of an outwardly rectifying Cl− current, with conductance of 1.6 nS, sensitive to niflumic acid and 5-nitro-2-(3-phenylpropylamino)benzoic acid, followed at H-18% by an outwardly rectifying K+ current with conductance of 4.1 nS, inhibited by clofilium but insensitive to the typical K+ channel blockers. With 200 nM Ca2+ in the patch pipette, whole cell currents activated at H-3% and at H-13% cells depolarized from −77 to −63 mV. A K+ current activated at H-1%, showing a rapid increase in conductance, suppressed by charybdotoxin and insensitive to clofilium. These results show the operation of two different K+ channels in response to GOR in the same cell type, activated by Ca2+ and osmolarity and with different osmolarity activation thresholds. Taurine and glutamate efflux, monitored by labeled tracers, showed delayed osmolarity thresholds of H-39 and H-33%, respectively. This observation clearly separates the Cl− and amino acid osmosensitive pathways. The delayed amino acid efflux may contribute to counteract swelling at more stringent osmolarity reductions.

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Effects of ginsenosides Re and Rg3 on intracellular redox state and cell proliferation in C6 glioma cells

Chinese Medicine ◽

10.1186/1749-8546-3-8 ◽

2008 ◽

Vol 3 (1) ◽

pp. 8 ◽

Cited By ~ 10

Author(s):

Wai Ng ◽

Mildred S Yang

Keyword(s):

Cell Proliferation ◽

Redox State ◽

Glioma Cells ◽

C6 Glioma ◽

C6 Glioma Cells ◽

Intracellular Redox

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Protein kinase C isoform ? overexpression in C6 glioma cells and its role in cell proliferation

Journal of Neuro-Oncology ◽

10.1007/bf01052840 ◽

1995 ◽

Vol 24 (3) ◽

pp. 241-250 ◽

Cited By ~ 29

Author(s):

Gordon H. Baltuch ◽

Nora P. Dooley ◽

Klara M. Rostworowski ◽

Jean -Guy Villemure ◽

Voon Wee Yong

Keyword(s):

Cell Proliferation ◽

Protein Kinase C ◽

Protein Kinase ◽

Glioma Cells ◽

C6 Glioma ◽

C6 Glioma Cells ◽

Kinase C

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The effect of yacon (Samallanthus sonchifolius) ethanol extract on cell proliferation and migration of C6 glioma cells stimulated with fetal bovine serum

Nutrition Research and Practice ◽

10.4162/nrp.2015.9.3.256 ◽

2015 ◽

Vol 9 (3) ◽

pp. 256 ◽

Cited By ~ 4

Author(s):

Kang Pa Lee ◽

Nan Hee Choi ◽

Jin Teak Kim ◽

In-Sik Park

Keyword(s):

Cell Proliferation ◽

Fetal Bovine Serum ◽

Glioma Cells ◽

Ethanol Extract ◽

C6 Glioma ◽

C6 Glioma Cells ◽

Cell Proliferation And Migration ◽

Fetal Bovine ◽

And Migration ◽

Proliferation And Migration

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Reduced tumorigenicity of rat glioma cells in the brain when mediated by hygromycin phosphotransferase

Journal of Neurosurgery ◽

10.3171/jns.2001.94.4.0596 ◽

2001 ◽

Vol 94 (4) ◽

pp. 596-604 ◽

Cited By ~ 6

Author(s):

Adília Hormigo ◽

David R. Friedlander ◽

Perry A. Brittis ◽

David Zagzag ◽

Martin Grumet

Keyword(s):

Cell Proliferation ◽

Rat Brain ◽

Glioma Cells ◽

C6 Glioma ◽

C6 Glioma Cells ◽

C6 Cells ◽

Content Type ◽

Hygromycin Phosphotransferase ◽

The Brain ◽

Fine Print

Object. A variant of C6 glioma cells, C6R-G/H cells express hygromycin phosphotransferase (HPT) and appear to have reduced tumorigenicity in the embryonic brain. The goal of this study was to investigate their reduced capacity to generate tumors in the adult rat brain. Methods. Cell lines were implanted into rat brains and tumorigenesis was evaluated. After 3 weeks, all rats with C6 cells showed signs of neurological disease, whereas rats with C6R-G/H cells did not and were either killed then or allowed to survive until later. Histological studies were performed to analyze tumor size, malignancy, angiogenesis, and cell proliferation. Cells isolated from rat brain tumors were analyzed for mutation to HPT by testing their sensitivity to hygromycin. Conclusions. The results indicate that HPT suppresses tumor formation. Three weeks after implantation, only 44% of animals implanted with C6R-G/H cells developed tumors, whereas all animals that received C6 glioma cells developed high-grade gliomas. The C6R-G/H cells filled a 20-fold smaller maximal cross-sectional area than the C6 cells, and exhibited less malignant characteristics, including reduced angiogenesis, mitosis, and cell proliferation. Similar results were obtained in the brain of nude rats, indicating that the immune system did not play a significant role in suppressing tumor growth. The combination of green fluorescent protein (GFP) and HPT was more effective in suppressing tumorigenesis than either plasmid by itself, indicating that the GFP may protect against inactivation of the HPT. Interestingly, hygromycin resistance was lost in tumor cells that were recovered from a group of animals in which C6R-G/H cells formed tumors, confirming the correlation of HPT with reduced tumorigenicity.

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