Particular sensitivity to calcium channel blockers of the fast inward voltage‐dependent sodium current involved in the invasive properties of a metastastic breast cancer cell line

Roger, Sébastien; Guennec, Jean‐Yves Le; Besson, Pierre

doi:10.1038/sj.bjp.0705649

Cited by 49 publications

(30 citation statements)

References 21 publications

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“…A fast inward Na + current was found in the very aggressive and metastatic MDA-MB-231 cell line that was absent in more indolent MCF-7 cells [26,27]. This current was TTX-sensitive and addition of TTX significantly reduced invasion by MDA-MB-231 cells [26].…”

Section: Voltage-sensitive Sodium Channelsmentioning

confidence: 91%

Voltage-sensitive ion channels and cancer

Fiske

Fomin

Brown

et al. 2006

Cancer Metastasis Rev

126

103

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Plasma membrane voltage-sensitive ion channels classically have been associated with a variety of inherited diseases or "channelopathies" that range in the severity of symptoms from mild to lethal. Ion channels are found throughout the body and are responsible for facilitated diffusion of ions down the electrochemical gradient across cells membranes in various tissues. Voltage-sensitive ion channels open in response to changes in the membrane potential and are primarily found in excitable cells and tissues. Potassium, calcium, and sodium channels play critical roles in the development of major diseases, such as hyperkalemia, epilepsy, congenital myotonia and several cardiac arrythmias. Recently, cancer studies have begun to define the role of voltage-sensitive ion channels in the progression of cancer to a more malignant phenotype. In cancer, the increased expression or increased kinetics of voltage-sensitive ion channels is associated with an increasing malignant potential as evinced by their role in cell proliferation, migration and survival; as such, these channels are becoming the targets of significant drug development efforts to block or reduce voltage-sensitive ion channel activity in order to prevent or combat malignant disease.

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Section: Voltage-sensitive Sodium Channelsmentioning

confidence: 91%

Voltage-sensitive ion channels and cancer

Fiske

Fomin

Brown

et al. 2006

Cancer Metastasis Rev

126

103

View full text Add to dashboard Cite

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“…The pharmacology of the sodium channel expressed in MDA-MB-231 cells is rather particular [41,45]. While its TTX sensitivity is consistent with a TTX-R isoform of the channel (see Table I), the channel is surprisingly also sensitive to some calcium channel blockers with IC 50 of 53.2 ± 3.6 µM for diltiazem and 37.6 ± 2.5 µM for verapamil, which are concentrations classically used to block calcium channels [45].…”

Section: Pharmacological Profile Of Vgnacmentioning

confidence: 99%

Voltage-Gated Sodium Channels: New Targets in Cancer Therapy?

Roger¹,

Potier²,

Vandier³

et al. 2006

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Early detection and treatment of cancers have increased survival and improved clinical outcome. The development of metastases is often associated with a poor prognostic of survival. Finding early markers of metastasis and developing new therapies against their development is a great challenge. Since a few years, there is more evidence that ionic channels are involved in the oncogenic process. Among these, voltagegated sodium channels expressed in non-nervous or non-muscular organs are often associated with the metastatic behaviour of different cancers. The aim of this review is to describe the current knowledge on the functional expression of voltage-gated sodium channels and their biological roles in different cancers such as prostate, breast, lung (small cells and non-small cells) and leukaemia. In the conclusion, we develop conceptual approaches to understand how such channels can be involved in the metastatic process and conclude that blockers targeted toward these channels are promising new therapeutic solutions against metastatic cancers.

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“…Neither is the STS-induced channel sensitive to amiloride (known to block weakly voltage dependent epithelial Na channels). Instead, 200 µM of the Ca channel blocker verapamil, also known to block Na and K channels Roger et al, 2004;Rolf et al, 2000;Yamagishi et al, 1995), almost completely abolished the current (Fig. 11A), leaving only a slowly activating current which most likely is mediated by another type of channel.…”

Section: Resultsmentioning

confidence: 99%

The role of ion channels and intracellular metal ions in apoptosis of Xenopus oocytes

Englund¹

2014

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Apoptosis is one type of programmed cell death, important during tissue development and to maintain the tissue homeostasis. Apoptosis comprises a complex network of internal signaling pathways, and an important part of this signaling network is the action of voltage‐gated ion channels. The aim of this thesis was to explore the role of ion channels and the role of intracellular metal ions during apoptosis in Xenopus laevis oocytes. The reasons for using these oocytes are that they are large, robust, easy to handle, and easy to study electrophysiologically. Apoptosis was induced either chemically by incubation of the oocytes in staurosporine (STS) or mechanically by centrifugation of the oocytes. Ion currents were measured by a two‐electrode voltage clamp technique, intracellular ion concentrations were measured either directly by in‐house developed K+‐selective microelectrodes or indirectly by the electrophysiological technique, and apoptosis was measured by caspase‐3 activation. Paper I describes that the intracellular K+ concentration was reduced by about 30 % during STS‐induced apoptosis. However, this reduction was prevented by excessive expression of exogenous ion channels. Despite the magnitude of the intracellular K+ concentration, either normal or reduced level, the oocytes displayed normal signs of apoptosis, suggesting that the intracellular K+ reduction was not required for the apoptotic process. Because the intracellular K+ concentration was not critical for apoptosis we searched for other ion fluxes by exploring the electrophysiological properties of X. laevis oocytes. Paper II, describes a non‐inactivating Na+ current activated at positive membrane voltages that was upregulated by a factor of five during STS‐induced apoptosis. By preventing influx of Na+, the apoptotic signaling network involving capsase‐3 was prevented. To molecularly identify this voltage‐gated Na channel, the X. tropicalis genome and conserved regions of the human SCNA genes were used as a map. Paper III, shows that the voltage‐gated Na channel corresponds to the SCN2A gene ortholog and that supression of this SCN2A ortholog using miRNA prevented cell death. In conclusion, this thesis work demonstrated that a voltage‐gated Na channel is critical for the apoptotic process in X. laevis oocytes by increasing the intracellular Na+ concentration

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Particular sensitivity to calcium channel blockers of the fast inward voltage‐dependent sodium current involved in the invasive properties of a metastastic breast cancer cell line

Cited by 49 publications

References 21 publications

Voltage-sensitive ion channels and cancer

Voltage-sensitive ion channels and cancer

Voltage-Gated Sodium Channels: New Targets in Cancer Therapy?

The role of ion channels and intracellular metal ions in apoptosis of Xenopus oocytes

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