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Voltage-gated sodium channel as a target for metastatic risk reduction with re-purposed drugs.

Koltai T - F1000Res (2015)

Bottom Line: To determine the exact role of sodium channel proteins in migration, invasion and metastasis and understand the possible anti-invasion and anti-metastatic activity of repurposed drugs with voltage gated sodium channel blocking properties.The following pharmaceuticals that fulfill the above mentioned effects, were found: phenytoin, carbamazepine, valproate, lamotrigine, ranolazine, resveratrol, ropivacaine, lidocaine, mexiletine, flunarizine, and riluzole.Each of them are independently described and analyzed.

View Article: PubMed Central - PubMed

Affiliation: Centro de Diagnóstico y Tratamiento de la Obra Social del Personal de la Industria de la Alimentación, Talar, Buenos Aires, C1122AAL, Argentina.

ABSTRACT

Objective: To determine the exact role of sodium channel proteins in migration, invasion and metastasis and understand the possible anti-invasion and anti-metastatic activity of repurposed drugs with voltage gated sodium channel blocking properties.

Material and methods: A review of the published medical literature was performed searching for pharmaceuticals used in daily practice, with inhibitory activity on voltage gated sodium channels. For every drug found, the literature was reviewed in order to define if it may act against cancer cells as an anti-invasion and anti-metastatic agent and if it was tested with this purpose in the experimental and clinical settings.

Results: The following pharmaceuticals that fulfill the above mentioned effects, were found: phenytoin, carbamazepine, valproate, lamotrigine, ranolazine, resveratrol, ropivacaine, lidocaine, mexiletine, flunarizine, and riluzole. Each of them are independently described and analyzed.

Conclusions: The above mentioned pharmaceuticals have shown anti-metastatic and anti-invasion activity and many of them deserve to be tested in well-planned clinical trials as adjunct therapies for solid tumors and as anti-metastatic agents. Antiepileptic drugs like phenytoin, carbamazepine and valproate and the vasodilator flunarizine emerged as particularly useful for anti-metastatic purposes.

No MeSH data available.


Related in: MedlinePlus

Proton extrusion through VGSC and NHE-1 (sodium hydrogen exchanger-1) produces acidification of extracellular matrix surrounding the cellular membrane (yellow area in the figure).(Brisson 201339; Gillet 200940). Acidification activates cathepsine degradation of the extracellular matrix.
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f4: Proton extrusion through VGSC and NHE-1 (sodium hydrogen exchanger-1) produces acidification of extracellular matrix surrounding the cellular membrane (yellow area in the figure).(Brisson 201339; Gillet 200940). Acidification activates cathepsine degradation of the extracellular matrix.

Mentions: An important location of VGSCs in cancer cells is in a cellular region directly involved in migration and invasion: the invadopodia. Invadopodias are protrusions of the plasma membrane, rich in actin that are strongly related to degradation of the extracellular matrix (ECM).Figure 4 andFigure 5 summarize how invadopodia works and the relation between VGSC and invadopodia.


Voltage-gated sodium channel as a target for metastatic risk reduction with re-purposed drugs.

Koltai T - F1000Res (2015)

Proton extrusion through VGSC and NHE-1 (sodium hydrogen exchanger-1) produces acidification of extracellular matrix surrounding the cellular membrane (yellow area in the figure).(Brisson 201339; Gillet 200940). Acidification activates cathepsine degradation of the extracellular matrix.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4920216&req=5

f4: Proton extrusion through VGSC and NHE-1 (sodium hydrogen exchanger-1) produces acidification of extracellular matrix surrounding the cellular membrane (yellow area in the figure).(Brisson 201339; Gillet 200940). Acidification activates cathepsine degradation of the extracellular matrix.
Mentions: An important location of VGSCs in cancer cells is in a cellular region directly involved in migration and invasion: the invadopodia. Invadopodias are protrusions of the plasma membrane, rich in actin that are strongly related to degradation of the extracellular matrix (ECM).Figure 4 andFigure 5 summarize how invadopodia works and the relation between VGSC and invadopodia.

Bottom Line: To determine the exact role of sodium channel proteins in migration, invasion and metastasis and understand the possible anti-invasion and anti-metastatic activity of repurposed drugs with voltage gated sodium channel blocking properties.The following pharmaceuticals that fulfill the above mentioned effects, were found: phenytoin, carbamazepine, valproate, lamotrigine, ranolazine, resveratrol, ropivacaine, lidocaine, mexiletine, flunarizine, and riluzole.Each of them are independently described and analyzed.

View Article: PubMed Central - PubMed

Affiliation: Centro de Diagnóstico y Tratamiento de la Obra Social del Personal de la Industria de la Alimentación, Talar, Buenos Aires, C1122AAL, Argentina.

ABSTRACT

Objective: To determine the exact role of sodium channel proteins in migration, invasion and metastasis and understand the possible anti-invasion and anti-metastatic activity of repurposed drugs with voltage gated sodium channel blocking properties.

Material and methods: A review of the published medical literature was performed searching for pharmaceuticals used in daily practice, with inhibitory activity on voltage gated sodium channels. For every drug found, the literature was reviewed in order to define if it may act against cancer cells as an anti-invasion and anti-metastatic agent and if it was tested with this purpose in the experimental and clinical settings.

Results: The following pharmaceuticals that fulfill the above mentioned effects, were found: phenytoin, carbamazepine, valproate, lamotrigine, ranolazine, resveratrol, ropivacaine, lidocaine, mexiletine, flunarizine, and riluzole. Each of them are independently described and analyzed.

Conclusions: The above mentioned pharmaceuticals have shown anti-metastatic and anti-invasion activity and many of them deserve to be tested in well-planned clinical trials as adjunct therapies for solid tumors and as anti-metastatic agents. Antiepileptic drugs like phenytoin, carbamazepine and valproate and the vasodilator flunarizine emerged as particularly useful for anti-metastatic purposes.

No MeSH data available.


Related in: MedlinePlus