Riluzole: Anti‐invasive effects on rat prostate cancer cells under normoxic and hypoxic conditions

Abstract

Anti‐invasive effects of riluzole and ranolazine, a neuro‐protectant and an anti‐anginal drug, respectively, on Mat‐LyLu rat prostate cancer (PCa) cells were tested in vitro (a) at non‐toxic doses and (b) under both normoxic and hypoxic conditions, the latter common to growing tumours. Tetrodotoxin (TTX) was used as a positive control. Hypoxia had no effect on cell viability but reduced growth at 48 hours. Riluzole (5 μmol/L) or ranolazine (20 μmol/L) had no effect on cell viability or growth under normoxia or hypoxia over 24 hours. Matrigel invasion was not affected by hypoxia but inhibited by TTX, ranolazine and riluzole under a range of conditions. The expression of Nav1.7 mRNA, the prevailing, pro‐invasive voltage‐gated sodium channel α‐subunit (VGSCα), was up‐regulated by hypoxia. Riluzole had no effect on Nav1.7 mRNA expression in normoxia but significantly reduced it in hypoxia. VGSCα protein expression in plasma membrane was reduced in hypoxia; riluzole increased it but only under hypoxia. It was concluded (a) that riluzole and ranolazine have anti‐invasive effects on rat PCa cells and (b) that Nav1.7 mRNA and protein expression can be modulated by riluzole under hypoxia. Overall, therefore, riluzole and ranolazine may ultimately be “repurposed” as anti‐metastatic drugs against PCa.

potencial uso do riluzole no tratamento do câncer

“…Nestas condições, o riluzole possui a capacidade de se ligar ao receptor e estabilizar o canal em seu estado inativado. Esse tipo de receptor foi primeiramente descrito em câncer de próstata de rato e sua atividade promove comportamentos metastáticos e progressão do câncer de próstata 79 . Contudo, em estudo in vitro mais recente com uso de células cancerígenas Saúde Meio Ambient.…”

Neonatal NaV1.5 channels: pharmacological distinctiveness of a cancer‐related voltage‐gated sodium channel splice variant

“…We first tested 6 broad-spectrum non-selective NaV channel inhibitors: lidocaine, procaine, phenytoin, mexiletine, riluzole and ranolazine. All of these compounds have been shown to inhibit metastatic behaviour of prostate, breast and/or colon cancer cell lines (Baptista-Hon et al, 2014;Bugan et al, 2019;Chamaraux-Tran et al, 2018;Driffort et al, 2014;Fairhurst et al, 2015;Ma et al, 2016;Martin et al, 2015;Rizaner et al, 2020).…”

FimH and Type 1 Pili Mediated Tumor Cell Cytotoxicity by Uropathogenic Escherichia coli In Vitro

“…A trypan blue assay (0.1%) was used to determine cell death [ 48 ]. MDA-MB-231 and MCF-7 cells were plated into 35 mm falcon tissue culture dishes (Thermo Fisher Scientific Nunc A/S, Roskilde, Denmark) with a 5 × 10 4 cells/mL density and allowed to incubate overnight to settle before the application of the treatment.…”