{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T05:10:39Z","timestamp":1790485839695,"version":"4.1.0"},"reference-count":134,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2015,7,22]],"date-time":"2015-07-22T00:00:00Z","timestamp":1437523200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["f1000research.com"],"crossmark-restriction":false},"short-container-title":["F1000Res"],"abstract":"<ns4:p>\n                    <ns4:bold>Objective:<\/ns4:bold>\n                    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.\n                  <\/ns4:p>\n                  <ns4:p>\n                    <ns4:bold>Material and methods:<\/ns4:bold>\n                    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.\n                  <\/ns4:p>\n                  <ns4:p>\n                    <ns4:bold>Results:<\/ns4:bold>\n                    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.\n                  <\/ns4:p>\n                  <ns4:p>\n                    <ns4:bold>Conclusions:<\/ns4:bold>\n                    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.\n                  <\/ns4:p>","DOI":"10.12688\/f1000research.6789.1","type":"journal-article","created":{"date-parts":[[2015,7,22]],"date-time":"2015-07-22T06:25:07Z","timestamp":1437546307000},"page":"297","update-policy":"https:\/\/doi.org\/10.12688\/f1000research.crossmark-policy","source":"Crossref","is-referenced-by-count":44,"title":["Voltage-gated sodium channel as a target for metastatic risk reduction with re-purposed 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prevention.","volume":"4","author":"M Taketo","year":"2011","journal-title":"Cancer Prev Res (Phila)."},{"key":"ref-4","doi-asserted-by":"publisher","first-page":"431S-436S","DOI":"10.3945\/ajcn.113.071290","article-title":"Genistein inhibits human prostate cancer cell detachment, invasion, and metastasis.","volume":"100","author":"J Pavese","year":"2014","journal-title":"Am J Clin Nutr."},{"key":"ref-5","doi-asserted-by":"publisher","first-page":"806-25","DOI":"10.2174\/1871520614666140521121722","article-title":"From French Paradox to cancer treatment: anti-cancer activities and mechanisms of resveratrol.","volume":"14","author":"X Yang","year":"2014","journal-title":"Anticancer Agents Med Chem."},{"key":"ref-6","doi-asserted-by":"publisher","first-page":"926-57","DOI":"10.3390\/cancers6020926","article-title":"Transcription Factor STAT3 as a Novel Molecular Target for Cancer Prevention.","volume":"6","author":"A Xiong","year":"2014","journal-title":"Cancers (Basel)."},{"key":"ref-7","doi-asserted-by":"publisher","first-page":"581-95","DOI":"10.1016\/j.molonc.2014.01.005","article-title":"miR181b is induced by the chemopreventive polyphenol curcumin and inhibits breast cancer metastasis via down-regulation of the inflammatory cytokines CXCL1 and -2.","volume":"8","author":"E Kronski","year":"2014","journal-title":"Mol Oncol."},{"key":"ref-8","doi-asserted-by":"publisher","first-page":"441-7","DOI":"10.1097\/CCO.0000000000000098","article-title":"Aspirin in gastrointestinal oncology: new data on an old friend.","volume":"26","author":"R Langley","year":"2014","journal-title":"Curr Opin Oncol."},{"key":"ref-9","doi-asserted-by":"publisher","first-page":"132-7","DOI":"10.1691\/ph.2014.3794","article-title":"Cyclooxygenase-2 inhibitor celecoxib suppresses invasion and migration of nasopharyngeal carcinoma cell lines through a decrease in matrix metalloproteinase-2 and -9 activity.","volume":"69","author":"W Li","year":"2014","journal-title":"Pharmazie."},{"key":"ref-10","doi-asserted-by":"publisher","first-page":"234-40","DOI":"10.1002\/ijc.28947","article-title":"The reversible P2Y12 inhibitor ticagrelor inhibits metastasis and improves survival in mouse models of cancer.","volume":"136","author":"S Gebremeskel","year":"2015","journal-title":"Int J Cancer."},{"key":"ref-11","doi-asserted-by":"publisher","first-page":"5572-9","DOI":"10.1016\/j.biomaterials.2014.03.047","article-title":"Effect of biodegradability on CXCR4 antagonism, transfection efficacy and antimetastatic activity of polymeric Plerixafor.","volume":"35","author":"J Li","year":"2014","journal-title":"Biomaterials."},{"key":"ref-12","doi-asserted-by":"publisher","first-page":"4344","DOI":"10.1038\/srep04344","article-title":"Nitric oxide inhibits hetero-adhesion of cancer cells to endothelial cells: restraining circulating tumor cells from initiating metastatic cascade.","volume":"4","author":"Y Lu","year":"2014","journal-title":"Sci Rep."},{"key":"ref-13","doi-asserted-by":"publisher","first-page":"289-98","DOI":"10.1208\/s12248-013-9559-2","article-title":"Synthesis, spectral characterization, and in vitro cellular activities of metapristone, a potential cancer metastatic chemopreventive agent derived from mifepristone (RU486).","volume":"16","author":"J Wang","year":"2014","journal-title":"AAPS J."},{"key":"ref-14","doi-asserted-by":"publisher","first-page":"1945-57","DOI":"10.1158\/0008-5472.CAN-13-2045","article-title":"Vaccine-mediated immunotherapy directed against a transcription factor driving the metastatic process.","volume":"74","author":"A Ardiani","year":"2014","journal-title":"Cancer Res."},{"key":"ref-15","first-page":"962-8","article-title":"Thiabendazole, a well-known antifungal drug, exhibits anti-metastatic melanoma B16F10 activity via inhibiting VEGF expression and inducing apoptosis.","volume":"68","author":"J Zhang","year":"2013","journal-title":"Pharmazie."},{"key":"ref-16","doi-asserted-by":"crossref","first-page":"1449-60","DOI":"10.18632\/oncotarget.1201","article-title":"Zoledronic acid inhibits macrophage\/microglia-assisted breast cancer cell invasion.","volume":"4","author":"E Rietk\u00f6tter","year":"2013","journal-title":"Oncotarget."},{"key":"ref-17","doi-asserted-by":"publisher","first-page":"15-26","DOI":"10.1517\/14712598.2013.843667","article-title":"Molecular target therapy for bone metastasis: starting a new era with denosumab, a RANKL inhibitor.","volume":"14","author":"C Rolfo","year":"2014","journal-title":"Expert Opin Biol Ther."},{"key":"ref-18","article-title":"NCT01952054, NCT01951586, NCT02129699"},{"key":"ref-19","doi-asserted-by":"publisher","first-page":"2577-2589","DOI":"10.1113\/jphysiol.2011.224204","article-title":"Voltage-gated sodium channels at 60: structure, function and pathophysiology.","volume":"590","author":"W Catterall","year":"2012","journal-title":"J Physiol."},{"key":"ref-20","doi-asserted-by":"publisher","first-page":"43-60","DOI":"10.1016\/S0065-7743(08)00003-1","article-title":"Chapter 3 \u2013 Recent Advances in Voltage-Gated Sodium Channel Blockers: Therapeutic Potential as Drug Targets in the CNS.","volume":"43","author":"A Termin","year":"2008","journal-title":"Annu Rep Med Chem."},{"key":"ref-21","doi-asserted-by":"publisher","first-page":"352-361","DOI":"10.4161\/chan.21910","article-title":"Voltage-gated sodium channels and metastatic disease.","volume":"6","author":"W Brackenbury","year":"2012","journal-title":"Channels (Austin)."},{"key":"ref-22","doi-asserted-by":"publisher","first-page":"407-412","DOI":"10.4161\/chan.2.6.7429","article-title":"Interaction between voltage-gated sodium channels and the neurotoxin, tetrodotoxin.","volume":"2","author":"C Lee","year":"2008","journal-title":"Channels (Austin)."},{"key":"ref-23","doi-asserted-by":"publisher","first-page":"5381-9","DOI":"10.1158\/1078-0432.CCR-05-0327","article-title":"Voltage-gated sodium channel expression and potentiation of human breast cancer metastasis.","volume":"11","author":"S Fraser","year":"2005","journal-title":"Clin Cancer Res."},{"key":"ref-24","doi-asserted-by":"publisher","first-page":"774-786","DOI":"10.1016\/j.biocel.2006.12.007","article-title":"Voltage-gated sodium channels potentiate the invasive capacities of human non-small-cell lung cancer cell lines.","volume":"39","author":"S Roger","year":"2007","journal-title":"Int J Biochem Cell Biol."},{"key":"ref-25","doi-asserted-by":"publisher","first-page":"153-163","DOI":"10.1007\/BF00234661","article-title":"Voltage-dependent sodium channels in human small-cell lung cancer cells: role in action potentials and inhibition by Lambert-Eaton syndrome IgG.","volume":"143","author":"J Blandino","year":"1995","journal-title":"J Membr Biol."},{"key":"ref-26","doi-asserted-by":"publisher","first-page":"469-478","DOI":"10.1002\/jcp.20871","article-title":"Functional expression of voltage-gated sodium channels in primary cultures of human cervical cancer.","volume":"210","author":"D Diaz","year":"2007","journal-title":"J Cell Physiol."},{"key":"ref-27","doi-asserted-by":"publisher","first-page":"908-914","DOI":"10.1007\/s00424-003-1205-x","article-title":"Voltage-gated Na+ channels confer invasive properties on human prostate cancer cells.","volume":"447","author":"E Bennett","year":"2004","journal-title":"Pflugers Arch."},{"key":"ref-28","doi-asserted-by":"publisher","first-page":"1293-1299","DOI":"10.3892\/or_00000763","article-title":"Expression of voltage-gated sodium channel alpha subunit in human ovarian cancer.","volume":"23","author":"R Gao","year":"2010","journal-title":"Oncol Rep."},{"key":"ref-29","doi-asserted-by":"publisher","first-page":"6957-67","DOI":"10.1158\/0008-5472.CAN-10-1169","article-title":"Voltage-gated Na+ channel SCN5A is a key regulator of a gene transcriptional network that controls colon cancer invasion.","volume":"70","author":"C House","year":"2010","journal-title":"Cancer Res."},{"key":"ref-30","doi-asserted-by":"publisher","first-page":"191-194","DOI":"10.1016\/j.febslet.2004.05.063","article-title":"T-lymphocyte invasiveness: control by voltage-gated Na+ channel activity.","volume":"569","author":"S Fraser","year":"2004","journal-title":"FEBS Lett."},{"key":"ref-31","doi-asserted-by":"publisher","first-page":"193-202","DOI":"10.1097\/00006676-199403000-00009","article-title":"Inhibitory effect of calcium channel blockers on growth of pancreatic cancer cells.","volume":"9","author":"K Sato","year":"1994","journal-title":"Pancreas."},{"key":"ref-32","doi-asserted-by":"publisher","first-page":"1146-1159","DOI":"10.1016\/j.biocel.2005.12.003","article-title":"Human neoplastic mesothelial cells express voltage-gated sodium channels involved in cell motility.","volume":"38","author":"G Fulgenzi","year":"2006","journal-title":"Int J Biochem Cell Biol."},{"key":"ref-33","doi-asserted-by":"publisher","first-page":"290-294","DOI":"10.1016\/0014-5793(95)00772-2","article-title":"Differential expression of voltage-activated Na+ currents in two prostatic tumour cell lines: contribution to invasiveness in vitro.","volume":"369","author":"J Grimes","year":"1995","journal-title":"FEBS Lett."},{"key":"ref-34","first-page":"1213-1221","article-title":"Expression and functional analysis of Voltage-activated Na+ channels in human prostate cancer cell lines and their contribution to invasion in vitro.","volume":"150","author":"M Laniado","year":"1997","journal-title":"Am J Pathol."},{"key":"ref-35","doi-asserted-by":"publisher","first-page":"19-24","DOI":"10.1016\/S0014-5793(98)00050-7","article-title":"Sodium channel protein expression enhances the invasiveness of rat and human prostate cancer cells.","volume":"423","author":"P Smith","year":"1998","journal-title":"FEBS Lett."},{"key":"ref-36","doi-asserted-by":"publisher","first-page":"479-87","DOI":"10.1002\/jcp.10312","article-title":"Contribution of functional voltage-gated Na+ channel expression to cell behaviors involved in the metastatic cascade in rat prostate cancer: I. Lateral motility.","volume":"195","author":"S Fraser","year":"2003","journal-title":"J Cell Physiol."},{"key":"ref-37","doi-asserted-by":"publisher","first-page":"107-111","DOI":"10.1016\/j.bbamem.2003.07.001","article-title":"Involvement of a novel fast inward sodium current in the invasion capacity of a breast cancer cell line.","volume":"1616","author":"S Roger","year":"2003","journal-title":"Biochim Biophys Acta."},{"key":"ref-38","doi-asserted-by":"publisher","first-page":"137-41","DOI":"10.1111\/j.1742-7843.2012.00880.x","article-title":"Oxidative stress in the in vivo DMBA rat model of breast cancer: suppression by a voltage-gated sodium channel inhibitor (RS100642).","volume":"111","author":"K Batcioglu","year":"2012","journal-title":"Basic Clin Pharmacol Toxicol."},{"key":"ref-39","doi-asserted-by":"publisher","first-page":"4835-4842","DOI":"10.1242\/jcs.123901","article-title":"Nav1.5 Na+ channels allosterically regulate the NHE-1 exchanger and promote the activity of breast cancer cell invadopodia.","volume":"126","author":"L Brisson","year":"2013","journal-title":"J Cell Sci."},{"key":"ref-40","doi-asserted-by":"publisher","first-page":"8680-8691","DOI":"10.1074\/jbc.M806891200","article-title":"Voltage-gated Sodium Channel Activity Promotes Cysteine Cathepsin-dependent Invasiveness and Colony Growth of Human Cancer Cells.","volume":"284","author":"L Gillet","year":"2009","journal-title":"J Biol Chem."},{"key":"ref-41","doi-asserted-by":"publisher","first-page":"1730-1741","DOI":"10.1158\/0008-5472.CAN-10-1432","article-title":"An EGFR-Src-Arg-Cortactin pathway mediates functional maturation of invadopodia and breast cancer cell invasion.","volume":"71","author":"C Mader","year":"2011","journal-title":"Cancer Res."},{"key":"ref-42","doi-asserted-by":"publisher","first-page":"4227-35","DOI":"10.1158\/0008-5472.CAN-06-3928","article-title":"Cortactin is an essential regulator of matrix metalloproteinase secretion and extracellular matrix degradation in invadopodia.","volume":"67","author":"E Clark","year":"2007","journal-title":"Cancer Res."},{"key":"ref-43","doi-asserted-by":"publisher","first-page":"413-426","DOI":"10.1038\/nrm3141","article-title":"The \u2018ins\u2019 and \u2018outs\u2019 of podosomes and invadopodia: characteristics, formation and function.","volume":"12","author":"D Murphy","year":"2011","journal-title":"Nat Rev Mol Cell Biol."},{"key":"ref-44","doi-asserted-by":"publisher","first-page":"352-361","DOI":"10.1152\/physiol.00012.2006","article-title":"Cortactin: the gray eminence of the cytoskeleton.","volume":"21","author":"L Cosen-Binker","year":"2006","journal-title":"Physiology (Bethesda)."},{"key":"ref-45","doi-asserted-by":"publisher","first-page":"67-75","DOI":"10.1007\/s00232-005-0747-6","article-title":"Small-cell lung cancer (human): potentiation of endocytic membrane activity by voltage-gated Na+ channel expression in vitro.","volume":"204","author":"P Onganer","year":"2005","journal-title":"J Membr Biol."},{"key":"ref-46","doi-asserted-by":"publisher","first-page":"141-57","DOI":"10.1016\/S0014-4827(85)80044-6","article-title":"Rous sarcoma virus-transformed fibroblasts adhere primarily at discrete protrusions of the ventral membrane called podosomes.","volume":"159","author":"G Tarone","year":"1985","journal-title":"Exp Cell Res."},{"key":"ref-47","doi-asserted-by":"publisher","first-page":"317-323","DOI":"10.1083\/jcb.200312168","article-title":"Active Rho is localized to podosomes induced by oncogenic Src and is required for their assembly and function.","volume":"166","author":"R Berdeaux","year":"2004","journal-title":"J Cell Biol."},{"key":"ref-48","doi-asserted-by":"publisher","first-page":"539-547","DOI":"10.3892\/ijo.2013.2214","article-title":"The small GTPase RhoA regulates the expression and function of the sodium channel Nav1.5 in breast cancer cells.","volume":"44","author":"C Dulong","year":"2014","journal-title":"Int J Oncol."},{"key":"ref-49","doi-asserted-by":"publisher","first-page":"747-757","DOI":"10.1158\/0008-5472.CAN-10-2267","article-title":"Spatial regulation of RhoA activity during pancreatic cancer cell invasion driven by mutant p53.","volume":"71","author":"P Timpson","year":"2011","journal-title":"Cancer Res."},{"key":"ref-50","doi-asserted-by":"publisher","first-page":"16846-16860","DOI":"10.1074\/jbc.M110.187559","article-title":"Angiogenic functions of voltage-gated Na+ Channels in human endothelial cells: modulation of vascular endothelial growth factor (VEGF) signaling.","volume":"286","author":"P Andrikopoulos","year":"2011","journal-title":"J Biol Chem."},{"key":"ref-51","doi-asserted-by":"publisher","first-page":"86","DOI":"10.3389\/fncel.2015.00086","article-title":"Cancer as a channelopaty: ion channels and pumps in tumor development and progression.","volume":"9","author":"A Litan","year":"2015","journal-title":"Front Cell Neurosci."},{"key":"ref-52","doi-asserted-by":"crossref","first-page":"453-479","DOI":"10.1007\/s002100000319","article-title":"Structure, function and pharmacology of voltage-gated sodium channels.","volume":"362","author":"H Denac","year":"2000","journal-title":"Naunyn Schmiedebergs Arch Pharmacol."},{"key":"ref-53","doi-asserted-by":"crossref","first-page":"523-30","DOI":"10.1016\/S0022-3565(25)21797-9","article-title":"Characterization of the block of sodium channels by phenytoin in mouse neuroblastoma cells.","volume":"228","author":"N Matsuki","year":"1984","journal-title":"J Pharmacol Exp Ther."},{"key":"ref-54","doi-asserted-by":"crossref","first-page":"549-58","DOI":"10.1016\/S0026-895X(25)12546-7","article-title":"Voltage clamp analysis of the inhibitory actions of diphenylhydantoin and carbamazepine on voltage-sensitive sodium channels in neuroblastoma cells.","volume":"27","author":"M Willow","year":"1985","journal-title":"Mol Pharmacol."},{"key":"ref-55","first-page":"460-2","article-title":"Phenytoin-induced lymphadenopathy.","volume":"17","author":"T Schwinghammer","year":"1983","journal-title":"Drug Intell Clin Pharm."},{"key":"ref-56","doi-asserted-by":"publisher","first-page":"803-8","DOI":"10.1093\/jnci\/81.10.803","article-title":"Cancer among epileptic patients exposed to anticonvulsant drugs.","volume":"81","author":"J Olsen","year":"1989","journal-title":"J Natl Cancer Inst."},{"key":"ref-57","doi-asserted-by":"publisher","first-page":"176-9","DOI":"10.1007\/BF00205612","article-title":"Effects of phenytoin on cell-mediated immunity.","volume":"26","author":"Y Okamoto","year":"1988","journal-title":"Cancer Immunol Immunother."},{"key":"ref-58","doi-asserted-by":"publisher","first-page":"27-32","DOI":"10.1016\/S0934-8832(11)80134-4","article-title":"The effect of phenytoin on collagenase and gelatinase activities in UMR 106-01 rat osteoblastic osteosarcoma cells.","volume":"10","author":"A Vernillo","year":"1990","journal-title":"Matrix."},{"key":"ref-59","doi-asserted-by":"publisher","first-page":"107-12","DOI":"10.1002\/jso.2930490209","article-title":"Search for anti-metastatic therapy: effects of phenytoin on B16 melanoma metastasis.","volume":"49","author":"M Dyce","year":"1992","journal-title":"J Surg Oncol."},{"key":"ref-60","doi-asserted-by":"publisher","first-page":"603-615","DOI":"10.1007\/s10549-012-2102-9","article-title":"Therapeutic potential for phenytoin: targeting Nav 1.5 sodium channels to reduce migration and invasion in metastatic breast cancer.","volume":"134","author":"M Yang","year":"2012","journal-title":"Breast Cancer Res Treat."},{"key":"ref-61","first-page":"756-765","article-title":"Frequency and voltage dependent inhibition of type IIA Na+ channels, expressed in a mammalian cell line by local anesthetic, antiarrhytmic and anticonvulsivant drugs.","volume":"40","author":"D Ragsdale","year":"1991","journal-title":"Mol Pharmacol."},{"key":"ref-62","first-page":"2045-8","article-title":"Inhibition by anticonvulsants of prostate-specific antigen and interleukin-6 secretion by human prostate cancer cells.","volume":"21","author":"M Abdul","year":"2001","journal-title":"Anticancer Res."},{"key":"ref-63","doi-asserted-by":"publisher","first-page":"146-55","DOI":"10.1177\/1933719114549853","article-title":"Phenytoin is an estrogen receptor \u03b1-selective modulator that interacts with helix 12.","volume":"22","author":"A Fadiel","year":"2015","journal-title":"Reprod Sci."},{"key":"ref-64","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1186\/s12943-014-0277-x","article-title":"The sodium channel-blocking antiepileptic drug phenytoin inhibits breast tumour growth and metastasis.","volume":"14","author":"M Nelson","year":"2015","journal-title":"Mol Cancer."},{"key":"ref-65","doi-asserted-by":"publisher","first-page":"43-50","DOI":"10.1007\/s00210-010-0519-4","article-title":"5,5-Diphenyl-2-thiohydantoin-N10 (DPTH-N10) suppresses proliferation of cultured colon cancer cell line COLO-205 by inhibiting DNA synthesis and activating apoptosis.","volume":"382","author":"T Lee","year":"2010","journal-title":"Naunyn Schmiedebergs Arch Pharmacol."},{"key":"ref-66","doi-asserted-by":"publisher","first-page":"294-305","DOI":"10.1016\/j.canlet.2008.06.016","article-title":"Anti-angiogenic action of 5,5-diphenyl-2-thiohydantoin-N10 (DPTH-N10).","volume":"271","author":"Y Liu","year":"2008","journal-title":"Cancer Lett."},{"key":"ref-67","doi-asserted-by":"publisher","first-page":"181-187","DOI":"10.3816\/CGC.2003.n.028","article-title":"Therapeutic approaches targeting prostate cancer progression using novel voltage-gated ion channel blockers.","volume":"2","author":"R Sikes","year":"2003","journal-title":"Clin Prostate Cancer."},{"key":"ref-68","first-page":"1149-54","article-title":"Voltage-gated sodium channel blockers as cytostatic inhibitors of the androgen-independent prostate cancer cell line PC-3.","volume":"2","author":"J Anderson","year":"2003","journal-title":"Mol Cancer Ther."},{"key":"ref-69","first-page":"4816-22","article-title":"Additivity of dilantin and vinblastine inhibitory effects on microtubule assembly.","volume":"59","author":"S Lobert","year":"1999","journal-title":"Cancer Res."},{"key":"ref-70","doi-asserted-by":"publisher","first-page":"183-8","DOI":"10.1038\/bjc.1996.33","article-title":"Modulation of vinblastine cytotoxicity by dilantin (phenytoin) or the protein phosphatase inhibitor okadaic acid involves the potentiation of anti-mitotic effects and induction of apoptosis in human tumour cells.","volume":"73","author":"K Kawamura","year":"1996","journal-title":"Br J Cancer."},{"key":"ref-71","doi-asserted-by":"crossref","first-page":"829-35","DOI":"10.1016\/S0022-3565(25)38428-4","article-title":"Lamotrigine, phenytoin and carbamazepine interactions on the sodium current present in N4TG1 mouse neuroblastoma cells.","volume":"266","author":"D Lang","year":"1993","journal-title":"J Pharmacol Exp Ther."},{"key":"ref-72","doi-asserted-by":"publisher","first-page":"PL79-83","DOI":"10.1016\/0024-3205(92)90104-W","article-title":"Segregation of the growth slowing effects of valproic acid from phenytoin and carbamazepine on lymphoid tumor cells.","volume":"50","author":"T Tittle","year":"1992","journal-title":"Life Sci."},{"key":"ref-73","doi-asserted-by":"publisher","first-page":"406-409","DOI":"10.1056\/NEJM198202183060707","article-title":"Transient antibody deficiency and abnormal t-suppressor cells induced by\u00a0phenytoin.","volume":"306","author":"H Dosch","year":"1982","journal-title":"N Engl J Med."},{"key":"ref-74","first-page":"273-85","article-title":"Depression of immune competence by phenytoin and carbamazepine. Studies in vivo and in vitro.","volume":"20","author":"T Sorrell","year":"1975","journal-title":"Clin Exp Immunol."},{"key":"ref-75","doi-asserted-by":"publisher","first-page":"228-31","DOI":"10.1016\/S0140-6736(76)91028-X","article-title":"IgA deficiency, epilepsy, and hydantoin medication.","volume":"2","author":"A Fontana","year":"1976","journal-title":"Lancet."},{"key":"ref-76","doi-asserted-by":"crossref","first-page":"147-157","DOI":"10.1177\/096032718500400205","article-title":"Effect of chronic anticonvulsant monotherapy on lymphocyte subpopulations in adult epileptic patients.","volume":"4","author":"M Marcoli","year":"1985","journal-title":"Hum Toxicol."},{"key":"ref-77","doi-asserted-by":"publisher","first-page":"691-9","DOI":"10.1007\/s00204-013-1183-5","article-title":"Inhibition of tumour spheroid-induced prometastatic intravasation gates in the lymph endothelial cell barrier by carbamazepine: drug testing in a 3D model.","volume":"88","author":"M Teichmann","year":"2014","journal-title":"Arch Toxicol."},{"key":"ref-78","doi-asserted-by":"publisher","first-page":"55-64","DOI":"10.1097\/CEJ.0b013e32834a7e6f","article-title":"Long-term antiepileptic treatment with histone deacetylase inhibitors may reduce the risk of prostate cancer.","volume":"21","author":"M Stettner","year":"2012","journal-title":"Eur J Cancer Prev."},{"key":"ref-79","doi-asserted-by":"publisher","first-page":"165-71","DOI":"10.1007\/s11010-010-0651-y","article-title":"Carbamazepine promotes Her-2 protein degradation in breast cancer cells by modulating HDAC6 activity and acetylation of Hsp90.","volume":"348","author":"Q Meng","year":"2011","journal-title":"Mol Cell Biochem."},{"key":"ref-80","first-page":"967-73","article-title":"[Inhibitory effect of carbamazepine on proliferation of estrogen-dependent breast cancer cells].","volume":"25","author":"Q Meng","year":"2006","journal-title":"Ai Zheng."},{"key":"ref-81","doi-asserted-by":"publisher","first-page":"597-610","DOI":"10.1017\/S1461145707008346","article-title":"The synergistic inhibitory actions of oxcarbazepine on voltage-gated sodium and potassium currents in differentiated NG108-15 neuronal cells and model neurons.","volume":"11","author":"C Huang","year":"2008","journal-title":"Int J Neuropsychopharmacol."},{"key":"ref-82","doi-asserted-by":"publisher","first-page":"3107-3115","DOI":"10.1016\/j.lfs.2005.01.003","article-title":"Carbamazepine is an inhibitor of histone deacetylases.","volume":"76","author":"A Beutler","year":"2005","journal-title":"Life Sci."},{"key":"ref-83","first-page":"37-49","article-title":"Valproic acid, a molecular lead to multiple regulatory pathways.","volume":"53","author":"M Kostrouchov\u00e1","year":"2007","journal-title":"Folia Biol (Praha)."},{"key":"ref-84","doi-asserted-by":"publisher","first-page":"3378-93","DOI":"10.2174\/138161207782360528","article-title":"Valproic acid as 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Schmeel","year":"2015","journal-title":"Anticancer Res."},{"key":"ref-104","doi-asserted-by":"publisher","first-page":"597-607","DOI":"10.1007\/s10495-010-0454-3","article-title":"The Ca2+ channel blocker flunarizine induces caspase-10-dependent apoptosis in Jurkat T-leukemia cells.","volume":"15","author":"D Conrad","year":"2010","journal-title":"Apoptosis."},{"key":"ref-105","doi-asserted-by":"publisher","first-page":"17-24","DOI":"10.1111\/j.1600-0625.1993.tb00194.x","article-title":"Inhibition of melanoma cell directional migration in vitro via different cellular targets.","volume":"2","author":"R Fink-Puches","year":"1993","journal-title":"Exp Dermatol."},{"key":"ref-106","doi-asserted-by":"publisher","first-page":"311-9","DOI":"10.1097\/00008390-199510000-00003","article-title":"Correlation of melanoma cell motility and invasion in vitro.","volume":"5","author":"R Hofmann-Wellenhof","year":"1995","journal-title":"Melanoma 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Kavanagh","year":"1993","journal-title":"Br J Cancer."},{"key":"ref-117","first-page":"229-34","article-title":"Effects of a calcium-antagonist (flunarizine) on the in vitro growth of B16 mouse melanoma cells.","volume":"4","author":"M Sezzi","year":"1984","journal-title":"Anticancer Res."},{"key":"ref-118","doi-asserted-by":"publisher","first-page":"1763-1755","DOI":"10.1038\/sj.cdd.4401863","article-title":"Flunarizine induces Nrf2-mediated transcriptional activation of heme oxygenase-1 in protection of auditory cells from cisplatin.","volume":"13","author":"H So","year":"2006","journal-title":"Cell Death Differ."},{"key":"ref-119","doi-asserted-by":"publisher","DOI":"10.1038\/srep07201","article-title":"HER2 confers drug resistance of human breast cancer cells through activation of NRF2 by direct interaction.","volume":"4","author":"H Kang","year":"2014","journal-title":"Sci 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Biol."},{"key":"ref-132","doi-asserted-by":"publisher","first-page":"2338-2351","DOI":"10.1002\/ijc.28890","article-title":"The sodium channel \u03b21 subunit mediates outgrowth of neurite-like processes on breast cancer cells and promotes tumour growth and metastasis.","volume":"135","author":"M Nelson","year":"2014","journal-title":"Int J Cancer."},{"key":"ref-133","doi-asserted-by":"publisher","first-page":"2070-2076","DOI":"10.1038\/onc.2010.574","article-title":"NaV1.5 enhances breast cancer cell invasiveness by increasing NHE1-dependent H+ efflux in caveolae.","volume":"30","author":"L Brisson","year":"2011","journal-title":"Oncogene."},{"key":"ref-134","doi-asserted-by":"publisher","first-page":"55-64","DOI":"10.1097\/CEJ.0b013e32834a7e6f","article-title":"Long-term antiepileptic treatment with histone deacetylase inhibitors may reduce the risk of prostate cancer.","volume":"21","author":"M Stettner","year":"2012","journal-title":"Eur J Cancer 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