Voltage-dependent K+ channels as oncotargets in malignant gliomas

Lefranc, Florence; Pouleau, Henri-Benjamin; Rynkowski, Michał; Witte, Olivier De

doi:10.18632/oncotarget.514

Cited by 10 publications

(15 citation statements)

References 9 publications

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“…UNBS1450 markedly decreases intracellular ATP concentration in glioma cells, disorganizing the actin cytoskeleton, and leads to autophagic cell death in glioma cells overexpressing Na + /K + ‐ATPase α 1 . The treatment of Na + /K + ‐ATPase ligands such as UNBS1450 reduces glioblastoma cell migration and induces autophagy . Joseph et al .…”

Section: Preclinical Evidence and Potential Mechanisms For Na+/k+‐atpmentioning

confidence: 99%

“…The treatment of Na + /K + -ATPase ligands such as UNBS1450 reduces glioblastoma cell migration and induces autophagy. 64,65 Joseph et al 66 found that treatment of digoxin through the inhibition of hypoxia-inducible factor (HIF)1a inhibited mesenchymal transition and invasion in glioblastoma SNB75 and U87 cells. Wolle et al 67 reported that ouabain did not transactivate EGFR but inhibited its effect via promotion of the activation of PI3K/Akt and ERK1/2 in medulloblastoma cells.…”

Section: Brain Cancermentioning

confidence: 99%

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Targeting Na⁺/K⁺‐translocating adenosine triphosphatase in cancer treatment

Durlacher

Chow

Chen

et al. 2015

Clin Exp Pharma Physio

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Summary The Na+/K+‐translocating adenosine triphosphatase (ATPase) transports sodium and potassium across the plasma membrane and represents a potential target in cancer chemotherapy. Na+/K+‐ATPase belongs to the P‐type ATPase family (also known as E1–E2 ATPase), which is involved in transporting certain ions, metals, and lipids across the plasma membrane of mammalian cells. In humans, the Na+/K+‐ATPase is a binary complex of an α‐subunit that has four isoforms (α1–α4) and a β‐subunit that has three isoforms (β1–β3). This review aims to update our knowledge on the role of Na+/K+‐ATPase in cancer development and metastasis, as well as on how Na+/K+‐ATPase inhibitors kill tumour cells. The Na+/K+‐ATPase has been found to be associated with cancer initiation, growth, development, and metastasis. Cardiac glycosides have exhibited anticancer effects in cell‐based and mouse studies via inhibition of the Na+/K+‐ATPase and other mechanisms. Na+/K+‐ATPase inhibitors may kill cancer cells via induction of apoptosis and autophagy, radical oxygen species production, and cell cycle arrest. They also modulate multiple signalling pathways that regulate cancer cell survival and death, which contributes to their antiproliferative activities in cancer cells. The clinical evidence supporting the use of Na+/K+‐ATPase inhibitors as anticancer drugs is weak. Several phase I and phase II clinical trials with digoxin, Anvirzel, and huachansu (an intravenous formulated extract of the venom of the wild toad), either alone or more often in combination with other anticancer agents, have shown acceptable safety profiles but limited efficacy in cancer patients. Well‐designed randomized clinical trials with reasonable sample sizes are certainly warranted to confirm the efficacy and safety of cardiac glycosides for the treatment of cancer.

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Section: Preclinical Evidence and Potential Mechanisms For Na+/k+‐atpmentioning

confidence: 99%

Section: Brain Cancermentioning

confidence: 99%

Targeting Na⁺/K⁺‐translocating adenosine triphosphatase in cancer treatment

Durlacher

Chow

Chen

et al. 2015

Clin Exp Pharma Physio

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“…Increasing evidence has demonstrated that a variety of K + channels, such as voltage-gated K + channels (K V ), calciumactivated K + channels (K Ca ) and ATP-sensitive K + channels (K ATP ) (8)(9)(10), are overexpressed in glioma biopsies and cultured cells. A previous study found a correlation between the activity of K ATP channels and proliferation of glioma cells and xenografted tumors (8).…”

Section: Introductionmentioning

confidence: 99%

Voltage-gated and ATP-sensitive K+ channels are associated with cell proliferation and tumorigenesis of human glioma

Xiang

et al. 2013

Oncology Reports

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Increasing evidence indicates that potassium (K+) channels play important roles in the growth and development of human cancer. In the present study, we investigated the contribution of and the mechanism by which K+ channels control the proliferation and tumor development of U87-MG human glioma cells. A variety of K+ channel blockers and openers were used to differentiate the critical subtype of K+ channels involved. The in vitro data demonstrated that selective blockers of voltage-gated K+ (K(V)) channels or ATP-sensitive K+ (K(ATP)) channels significantly inhibited the proliferation of U87-MG cells, blocked the cell cycle at the G0/G1 phase and induced apoptosis. In the U87-MG xenograft model in nude mice, K(V) or K(ATP) channel blockers markedly suppressed tumor growth in vivo. Furthermore, electrophysiological results showed that KV or KATP channel blockers inhibited K(V)/K(ATP) channel currents as well as cell proliferation and tumor growth over the same concentration range. In contrast, iberiotoxin, a selective blocker of calcium-activated K+ channels, had no apparent effect on the cell proliferation, cell cycle or apoptosis of U87-MG cells. In addition, the results of fluorescence assays indicated that blockers of K(V) or K(ATP) channels attenuated intracellular Ca2+ signaling by blocking Ca2+ influx in U87-MG cells. Taken together, these data suggest that K(V) and K(ATP) channels play important roles in the proliferation of U87-MG cells and that the influence of K(V) and K(ATP) channels may be mediated by a Ca2+-dependent mechanism.

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“…The majority of patients die within a year after diagnosis and less than 10% survive for more than 5 years [9]. High mortality from glioblastoma multiforme is explained by its high invasive activity [6,8].…”

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confidence: 99%

“…The fi rst evidence of Avastin effi ciency in malignant glioma appeared in 2005, but this drug was not used as the fi rst-line therapy in patients with new glioblastoma cases [9]. Signifi cant effi ciency of MAbE2Cx43 as monotherapy for poorly differentiated glioma necessitates evaluation of the effi ciency of these antibodies as a component of combined therapy together with drugs and radiotherapy recommended by WHO.…”

mentioning

confidence: 99%

Treatment of Poorly Differentiated Glioma Using a Combination of Monoclonal Antibodies to Extracellular Connexin-43 Fragment, Temozolomide, and Radiotherapy

et al. 2014

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Antitumor efficiencies of monoclonal antibodies to connexin-43 second extracellular loop (MAbE2Cx43), temozolomide, and fractionated γ-irradiation in the monotherapy mode and in several optimized combinations were studied in Wistar rats with induced C6 glioma. The survival of animals with glioma and the dynamics of intracerebral tumor development were evaluated by MRT. Temozolomide monotherapy (200 mg/m(2)) and isolated radiotherapy in a total dose of 36 Gy shifted the survival median from 28 days (no therapy) to 34 and 38 days, respectively; 100% animals died under conditions of temozolomide monotherapy and radiotherapy. Monotherapy with MAbE2Cx43 in a dose of 5 mg/kg led to significant regression of the tumor (according to MRT data), cure of 19.23% animals with glioma, and prolongation of the survival median to 39.5 days after tumor implantation. Combined therapy with MAbE2Cx43 and temozolomide completely abolished the antitumor effect (survival median 29 days). Treatment with MAbE2Cx43 in combination with radiotherapy was associated with mutual boosting of the therapeutic efficiencies, leading to a significant inhibition of tumor development and prolongation of the survival median to 60 days. The mechanism of tumorsuppressive activity of the antibodies could be due to connexon blockade in Cx43-positive glioma cells in the peritumor invasion zone. Higher efficiency of combined therapy was presumably due to the increase in blood-brain barrier permeability for antibodies after irradiation of the brain and to additional inhibitory effect of antibodies towards radioresistant migrating glioma cells. The results suggested that MAbE2Cx43 could be effective as the first-line drug in combined therapy for poorly differentiated gliomas.

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Voltage-dependent K+ channels as oncotargets in malignant gliomas

Cited by 10 publications

References 9 publications

Targeting Na⁺/K⁺‐translocating adenosine triphosphatase in cancer treatment

Targeting Na⁺/K⁺‐translocating adenosine triphosphatase in cancer treatment

Voltage-gated and ATP-sensitive K+ channels are associated with cell proliferation and tumorigenesis of human glioma

Treatment of Poorly Differentiated Glioma Using a Combination of Monoclonal Antibodies to Extracellular Connexin-43 Fragment, Temozolomide, and Radiotherapy

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Voltage-dependent K+ channels as oncotargets in malignant gliomas

Cited by 10 publications

References 9 publications

Targeting Na+/K+‐translocating adenosine triphosphatase in cancer treatment

Targeting Na+/K+‐translocating adenosine triphosphatase in cancer treatment

Voltage-gated and ATP-sensitive K+ channels are associated with cell proliferation and tumorigenesis of human glioma

Treatment of Poorly Differentiated Glioma Using a Combination of Monoclonal Antibodies to Extracellular Connexin-43 Fragment, Temozolomide, and Radiotherapy

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Targeting Na⁺/K⁺‐translocating adenosine triphosphatase in cancer treatment

Targeting Na⁺/K⁺‐translocating adenosine triphosphatase in cancer treatment