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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

Taroneet al.46 in 1985 reported the relation between the oncogenic Src and promotion of invadopodia.Berdeauxet al.47 reported that the small molecule GTPase Rho A activity is under control of oncogenic Src and localizes in the invadopodia complex and Durlonget al.48 (2013) showed that Rho-A regulates the expression and activity of NaV1.5 and found a positive feedback between NaV1.5 and Rho A in breast cancer cells. According to Timpsonet al.49, cooperation between mutant p53 and oncogenic Ras activates Rho-A.
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f6: Taroneet al.46 in 1985 reported the relation between the oncogenic Src and promotion of invadopodia.Berdeauxet al.47 reported that the small molecule GTPase Rho A activity is under control of oncogenic Src and localizes in the invadopodia complex and Durlonget al.48 (2013) showed that Rho-A regulates the expression and activity of NaV1.5 and found a positive feedback between NaV1.5 and Rho A in breast cancer cells. According to Timpsonet al.49, cooperation between mutant p53 and oncogenic Ras activates Rho-A.

Mentions: One possible relation between invadopodia-Src-VGSCs is described inFigure 6.


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

Koltai T - F1000Res (2015)

Taroneet al.46 in 1985 reported the relation between the oncogenic Src and promotion of invadopodia.Berdeauxet al.47 reported that the small molecule GTPase Rho A activity is under control of oncogenic Src and localizes in the invadopodia complex and Durlonget al.48 (2013) showed that Rho-A regulates the expression and activity of NaV1.5 and found a positive feedback between NaV1.5 and Rho A in breast cancer cells. According to Timpsonet al.49, cooperation between mutant p53 and oncogenic Ras activates Rho-A.
© Copyright Policy
Related In: Results  -  Collection

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

f6: Taroneet al.46 in 1985 reported the relation between the oncogenic Src and promotion of invadopodia.Berdeauxet al.47 reported that the small molecule GTPase Rho A activity is under control of oncogenic Src and localizes in the invadopodia complex and Durlonget al.48 (2013) showed that Rho-A regulates the expression and activity of NaV1.5 and found a positive feedback between NaV1.5 and Rho A in breast cancer cells. According to Timpsonet al.49, cooperation between mutant p53 and oncogenic Ras activates Rho-A.
Mentions: One possible relation between invadopodia-Src-VGSCs is described inFigure 6.

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