Therapeutic Value of Voltage-Gated Sodium Channel Inhibitors in Breast, Colorectal, and Prostate Cancer: A Systematic Review

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Martin, Fabiola ; Ufodiama, Chiedu ; Watt, Ian ; Bland, Martin ; Brackenbury, William J. (2015)
  • Publisher: Frontiers Media S.A.
  • Journal: Frontiers in Pharmacology, volume 6 (issn: 1663-9812, eissn: 1663-9812)
  • Related identifiers: pmc: PMC4714608, doi: 10.3389/fphar.2015.00273
  • Subject: colonic neoplasms | sodium channels | Review | breast neoplasms | Pharmacology | prostatic neoplasms | anticonvulsants

Although survival rates of breast, colon, and prostate cancers are improving, deaths from these tumors frequently occur due to metastasis. Voltage-gated Na+ channels (VGSCs) are membrane proteins, which regulate membrane current and cellular migration during nervous system organogenesis. VGSCs are also expressed in fibroblasts, immune cells, glia, and metastatic cancer cells. VGSCs regulate migration and invasion of breast, bowel, and prostate cancer cells, suggesting that they may be novel anti-metastatic targets. We conducted a systematic review of clinical and preclinical studies testing the effects of VGSC-inhibiting drugs in cancer. Two-hundred and four publications were identified, of which two human, two mouse, and 20 in vitro publications were included. In the clinical studies, the effect of these drugs on survival and metastatic relapse is not clear. The 22 preclinical studies collectively suggest that several VGSC-inhibiting drugs inhibit cancer proliferation, migration, and invasion. None of the human and only six of the preclinical studies directly investigated the effect of the drugs on VGSC activity. Studies were difficult to compare due to lack of standardized methodology and outcome measures. We conclude that the benefits of VGSC inhibitors require further investigation. Standardization of future studies and outcome measures should enable meaningful study comparisons.
  • References (68)
    68 references, page 1 of 7

    Abdul, M., and Hoosein, N. (2001). Inhibition by anticonvulsants of prostatespecific antigen and interleukin-6 secretion by human prostate cancer cells. Anticancer. Res. 21, 2045-2048.

    Abdul, M., and Hoosein, N. (2002). Voltage-gated sodium ion channels in prostate cancer: expression and activity. Anticancer. Res. 22, 1727-1730.

    Al Snafi, A. E., Yaseen, N. Y., and Al Shatry, M. M. (2014). Anticancer effect of sodium valpoate. Int. J. Pharm. Technol. Res. 7, 291-297.

    Anderson, J. D., Hansen, T. P., Lenkowski, P. W., Walls, A. M., Choudhury, I. M., Schenck, H. A., et al. (2003). Voltage-gated sodium channel blockers as cytostatic inhibitors of the androgen-independent prostate cancer cell line PC-3. Mol. Cancer Ther. 2, 1149-1154.

    Angelucci, A., Valentini, A., Millimaggi, D., Gravina, G. L., Miano, R., Dolo, V., et al. (2006). Valproic acid induces apoptosis in prostate carcinoma cell lines by activation of multiple death pathways. Anticancer. Drugs 17, 1141-1150. doi: 10.1097/01.cad.0000236302.89843.fc

    Baptista-Hon, D. T., Robertson, F. M., Robertson, G. B., Owen, S. J., Rogers, G. W., Lydon, E. L., et al. (2014). Potent inhibition by ropivacaine of metastatic colon cancer SW620 cell invasion and NaV1.5 channel function. Br. J. Anaesth. 113(Suppl. 1), i39-i48. doi: 10.1093/bja/aeu104

    Bennett, E. S., Smith, B. A., and Harper, J. M. (2004). Voltage-gated Na+ channels confer invasive properties on human prostate cancer cells. Pflugers. Arch. 447, 908-914. doi: 10.1007/s00424-003-1205-x

    Besson, P., Driffort, V., Bon, E., Gradek, F., Chevalier, S., and Roger, S. (2015). How do voltage-gated sodium channels enhance migration and invasiveness in cancer cells? Biochim. Biophys. Acta 1848, 2493-2501. doi: 10.1016/j.bbamem.2015.04.013

    Black, J. A., and Waxman, S. G. (2013). Non-canonical roles of voltage-gated sodium channels. Neuron 80, 280-291. doi: 10.1016/j.neuron.2013.09.012

    Brackenbury, W. J. (2012). Voltage-gated sodium channels and metastatic disease. Channels (Austin) 6, 352-361. doi: 10.4161/chan.21910

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