Inhibitory effect of calcium channel blockers on proliferation of human glioma cells<i>in vitro</i>

Kunert‐Radek, Jolanta; Stępień, H; Radek, A; Lysoń, Krzysztof; Pawlikowski, Marek

doi:10.1111/j.1600-0404.1989.tb03731.x

Cited by 28 publications

(19 citation statements)

References 16 publications

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“…In our earlier papers, we reported that the blockade of calcium channels by specific inhibitors, verapamil and nimodipine, suppressed in vitro the proliferation of rat pituitary tumoral cells [29], human glioma cells [30] and mouse spleen lymphocytes [31]. Calcium chloride tested at different concentrations stimulated [3H]thymidine in corporation into the D N A of rat pituitary tumor cells in a dose-dependent manner [29].…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Rat Pituitary Tumor Cell Proliferation by Benzodiazepines in vitro

Kunert‐Radek¹,

Stępień²,

Pawlikowski³

1994

Neuroendocrinology

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The effect of various benzodiazepines (peripheral-type receptor ligands: Ro 5-4864, PK 11135; central-type receptor ligands: clonazepam, Ro 15-1788, Ro 15-4513; mixed type: diazepam) on the proliferation of estrogen-induced rat pituitary prolactin-secreting tumor cells was studied in vitro. [³H]thymidine incorporation into DNA was used as an index of cell proliferation. It was found that tested peripheral- and mixed-type benzodiazepine receptor ligands significantly suppressed the pituitary cell proliferation in a dose-dependent manner (10^–4–10^–8M). The inhibitory effect of Ro 5-4864 was reversed by 5 × 10^–3M calcium chloride. On the other hand, central-type benzodiazepine receptor ligands suppressed tumor cell proliferation only at the highest concentration studied (10^–4 M). Our results indicate that benzodiazepines might exert an antiproliferative action on pituitary tumor cell growth, and that this effect seems to be a calcium-dependent process.

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Section: Discussionmentioning

confidence: 99%

Inhibition of Rat Pituitary Tumor Cell Proliferation by Benzodiazepines in vitro

Kunert‐Radek¹,

Stępień²,

Pawlikowski³

1994

Neuroendocrinology

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“…The existence of a novel Ca v 3.1 splice variant, and the fact that voltage-gated calcium channel inhibition decreases glioma cells proliferation (Kunert-Radek et al, 1989), suggest that regulation of T-type channel gene expression may contribute to the pathophysiology of certain tumors. …”

Section: Could There Be a Role For T-type Channels Inmentioning

confidence: 99%

Expression of T‐type calcium channel splice variants in human glioma

Latour

Louw

Beedle

et al. 2004

Glia

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In humans, three isoforms of the T-type (Ca(v)3.1) calcium-channel alpha(1) subunit have been reported as a result of alternate splicing of exons 25 and 26 in the III-IV linker region (Ca(v)3.1a, Ca(v)3.1b or Ca(v)3.1bc). In the present study, we report that human glioma express Ca(v)3.1 channels in situ, that splicing of these exons is uniquely regulated and that there is expression of a glioma-specific novel T-type variant (Ca(v)3.1ac). Seven human glioma samples were collected at surgery, RNA was extracted, and cDNA was produced for RT-PCR analysis. In addition, three glioma cell lines (U87, U563, and U251N), primary cultures of human fetal astrocytes, as well as adult and fetal human brain cDNA were used. Previously described Ca(v)3.1 splice variants were present in glioma samples, cultured cells and whole brain. Consistent with the literature, our results reveal that in the normal adult brain, Ca(v)3.1a transcripts predominate, while Ca(v)3.1b is mostly fetal-specific. RT-PCR results on glioma and glioma cell lines showed that Ca(v)3.1 expression in tumor cells resemble fetal brain expression pattern as Ca(v)3.1bc is predominantly expressed. In addition, we identified a novel splice variant, Ca(v)3.1ac, expressed in three glioma biopsies and one glioma cell line, but not in normal brain or fetal astrocytes. Transient expression of this variant demonstrates that Ca(v)3.1ac displays similar current-voltage and steady-state inactivation properties compared with Ca(v)3.1b, but a slower recovery from inactivation. Taken together, our data suggest glioma-specific Ca(v)3.1 gene regulation, which could possibly contribute to tumor pathogenesis.

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“…We examined both possibilities through biophysical recordings and the use of pharmacological blockers. Studies in human gliomas have demonstrated the expression of both L-type and T-type VGCCs (27,28), and data from our own laboratory suggest that these cells express TRPC channels, a nonselective cation channel that is permeable to calcium and has been implicated in store-operated calcium entry (50). We thus set out to determine whether one of these candidate channels was the calcium source for BK channels.…”

Section: Journal Of Biological Chemistry 31563mentioning

confidence: 99%

BK Channels Are Linked to Inositol 1,4,5-Triphosphate Receptors via Lipid Rafts

Weaver

Olsen

McFerrin

et al. 2007

Journal of Biological Chemistry

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Glioma cells prominently express a unique splice variant of a large conductance, calcium-activated potassium channel (BK channel). These channels transduce changes in intracellular calcium to changes of K ؉ conductance in the cells and have been implicated in growth control of normal and malignant cells. The Ca 2؉ increase that facilitates channel activation is thought to occur via activation of intracellular calcium release pathways or influx of calcium through Ca 2؉ -permeable ion channels. We show here that BK channel activation involves the activation of inositol 1,4,5-triphosphate receptors (IP 3 R), which localize near BK channels in specialized membrane domains called lipid rafts. Disruption of lipid rafts with methyl-␤-cyclodextrin disrupts the functional association of BK channel and calcium source resulting in a >50% reduction in K ؉ conductance mediated by BK channels. The reduction of BK current by lipid raft disruption was overcome by the global elevation of intracellular calcium through inclusion of 750 nM Ca 2؉ in the pipette solution, indicating that neither the calcium sensitivity of the channel nor their overall number was altered. Additionally, pretreatment of glioma cells with 2-aminoethoxydiphenyl borate to inhibit IP 3 Rs negated the effect of methyl-␤-cyclodextrin, providing further support that IP 3 Rs are the calcium source for BK channels. Taken together, these data suggest a privileged association of BK channels in lipid raft domains and provide evidence for a novel coupling of these Ca 2؉ -sensitive channels to their second messenger source.

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Inhibitory effect of calcium channel blockers on proliferation of human glioma cellsin vitro

Cited by 28 publications

References 16 publications

Inhibition of Rat Pituitary Tumor Cell Proliferation by Benzodiazepines in vitro

Inhibition of Rat Pituitary Tumor Cell Proliferation by Benzodiazepines in vitro

Expression of T‐type calcium channel splice variants in human glioma

BK Channels Are Linked to Inositol 1,4,5-Triphosphate Receptors via Lipid Rafts

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