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

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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Mood stabilizers have differential effects on endogenous ADP ribosylation in C6 glioma cells

European Journal of Pharmacology ◽

10.1016/0014-2999(96)00319-6 ◽

1996 ◽

Vol 309 (2) ◽

pp. 215-218 ◽

Cited By ~ 7

Author(s):

L.Trevor Young ◽

Caroline M. Woods

Keyword(s):

Glioma Cells ◽

C6 Glioma ◽

Mood Stabilizers ◽

C6 Glioma Cells ◽

Differential Effects ◽

Adp Ribosylation

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

Biochemical Society Transactions ◽

10.1042/bst0350391 ◽

2007 ◽

Vol 35 (2) ◽

pp. 391-395 ◽

Cited By ~ 8

Author(s):

T.M. Weiger ◽

S. Colombatto ◽

V. Kainz ◽

W. Heidegger ◽

M.A. Grillo ◽

...

Keyword(s):

Cell Proliferation ◽

Potassium Channel ◽

Glioma Cells ◽

C6 Glioma ◽

Antiproliferative Effect ◽

C6 Glioma Cells ◽

Decarboxylase Activity ◽

Channel Blockers ◽

Potassium Channel Blockers ◽

Internal Calcium

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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Radiosensitivity of glioma to Gamma Knife treatment enhanced in vitro and in vivo by RNA interfering Ku70 that is mediated by a recombinant adenovirus

Journal of Neurosurgery ◽

10.3171/2010.7.gks10972 ◽

2010 ◽

Vol 113 (Special_Supplement) ◽

pp. 228-235 ◽

Cited By ~ 4

Author(s):

Qiang Jia ◽

Yanhe Li ◽

Desheng Xu ◽

Zhenjiang Li ◽

Zhiyuan Zhang ◽

...

Keyword(s):

Western Blot ◽

Gamma Knife ◽

Blot Analysis ◽

Western Blot Analysis ◽

Glioma Cells ◽

C6 Glioma ◽

C6 Glioma Cells ◽

C6 Cells

Object The authors sought to evaluate modification of the radiation response of C6 glioma cells in vitro and in vivo by inhibiting the expression of Ku70. To do so they investigated the effect of gene transfer involving a recombinant replication-defective adenovirus containing Ku70 short hairpin RNA (Ad-Ku70shRNA) combined with Gamma Knife treatment (GKT). Methods First, Ad-Ku70shRNA was transfected into C6 glioma cells and the expression of Ku70 was measured using Western blot analysis. In vitro, phenotypical changes in C6 cells, including proliferation, cell cycle modification, invasion ability, and apoptosis were evaluated using the MTT (3′(4,5-dimethylthiazol-2-yl)2,5-diphenyltetrazolium bromide) assay, Western blot analysis, and cell flow cytometry. In vivo, parental C6 cells transfected with Ad-Ku70shRNA were implanted stereotactically into the right caudate nucleus in Sprague-Dawley rats. After GKS, apoptosis was analyzed using the TUNEL (terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate nick-end labeling) method. The inhibitory effects on growth and invasion that were induced by expression of proliferating cell nuclear antigen and matrix metalloproteinase–9 were determined using immunohistochemical analyses. Results The expression of Ku70 was clearly inhibited in C6 cells after transfection with Ad-Ku70shRNA. In vitro following transfection, the C6 cells showed improved responses to GKT, including suppression of proliferation and invasion as well as an increased apoptosis index. In vivo following transfection of Ad-Ku70shRNA, the therapeutic efficacy of GKT in rats with C6 gliomas was greatly enhanced and survival times in these animals were prolonged. Conclusions Our data support the potential for downregulation of Ku70 expression in enhancing the radiosensitivity of gliomas. The findings of our study indicate that targeted gene therapy–mediated inactivation of Ku70 may represent a promising strategy in improving the radioresponsiveness of gliomas to GKT.

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P2Y Receptor Activation Affects the Proliferation and Differentiation of Glial and Neuronal Cells: A Focus on Rat C6 Glioma Cells

Current Neuropharmacology ◽

10.2174/1570159043476837 ◽

2004 ◽

Vol 2 (2) ◽

pp. 207-220 ◽

Cited By ~ 8

Author(s):

Patrik Claes ◽

Herman Slegers

Keyword(s):

Neuronal Cells ◽

Glioma Cells ◽

Receptor Activation ◽

C6 Glioma ◽

C6 Glioma Cells ◽

P2y Receptor ◽

Proliferation And Differentiation ◽

Rat C6 Glioma

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Transfected Go1 alpha inhibits the calcium dependence of beta-adrenergic stimulated cAMP accumulation in C6 glioma cells.

Journal of Biological Chemistry ◽

10.1016/s0021-9258(18)52968-9 ◽

1993 ◽

Vol 268 (12) ◽

pp. 8980-8989

Author(s):

N. Charpentier ◽

L. Prézeau ◽

J. Carrette ◽

R. Bertorelli ◽

G. Le Cam ◽

...

Keyword(s):

Glioma Cells ◽

C6 Glioma ◽

C6 Glioma Cells ◽

Camp Accumulation ◽

Beta Adrenergic ◽

Calcium Dependence

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α-Conotoxins and α-Cobratoxin Promote, while Lipoxygenase and Cyclooxygenase Inhibitors Suppress the Proliferation of Glioma C6 Cells

Marine Drugs ◽

10.3390/md19020118 ◽

2021 ◽

Vol 19 (2) ◽

pp. 118

Author(s):

Tatiana I. Terpinskaya ◽

Alexey V. Osipov ◽

Elena V. Kryukova ◽

Denis S. Kudryavtsev ◽

Nina V. Kopylova ◽

...

Keyword(s):

Nicotinic Acetylcholine Receptors ◽

Acetylcholine Receptors ◽

Glioma Cells ◽

Nordihydroguaiaretic Acid ◽

C6 Glioma ◽

Cyclooxygenase Inhibitors ◽

C6 Glioma Cells ◽

C6 Cells ◽

Lipoxygenase Inhibitor ◽

Glioma C6

Among the brain tumors, glioma is the most common. In general, different biochemical mechanisms, involving nicotinic acetylcholine receptors (nAChRs) and the arachidonic acid cascade are involved in oncogenesis. Although the engagement of the latter in survival and proliferation of rat C6 glioma has been shown, there are practically no data about the presence and the role of nAChRs in C6 cells. In this work we studied the effects of nAChR antagonists, marine snail α-conotoxins and snake α-cobratoxin, on the survival and proliferation of C6 glioma cells. The effects of the lipoxygenase and cyclooxygenase inhibitors either alone or together with α-conotoxins and α-cobratoxin were studied in parallel. It was found that α-conotoxins and α-cobratoxin promoted the proliferation of C6 glioma cells, while nicotine had practically no effect at concentrations below 1 µL/mL. Nordihydroguaiaretic acid, a nonspecific lipoxygenase inhibitor, and baicalein, a 12-lipoxygenase inhibitor, exerted antiproliferative and cytotoxic effects on C6 cells. nAChR inhibitors weaken this effect after 24 h cultivation but produced no effects at longer times. Quantitative real-time polymerase chain reaction showed that mRNA for α4, α7, β2 and β4 subunits of nAChR were expressed in C6 glioma cells. This is the first indication for involvement of nAChRs in mechanisms of glioma cell proliferation.

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