Referenced in: none

Automatically associated channels: Nav1.2

Title: Voltage-gated sodium channel blockers as cytostatic inhibitors of the androgen-independent prostate cancer cell line PC-3.

Authors: James D Anderson, Todd P Hansen, Paul W Lenkowski, Alison M Walls, Indrani M Choudhury, Hilary A Schenck, Mati Friehling, Genevieve M Höll, Manoj K Patel, Robert A Sikes, Milton L Brown

Journal, date & volume: Mol. Cancer Ther., 2003 Nov , 2, 1149-54

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/14617788

Abstract
The recent discovery of sodium (Na(+)) channel expression in human prostate cancer (PCa) cells led us to investigate the potential use of neuronal Na(+) channel blockers as inhibitors of PCa cells. Our initial studies discovered two classes of Na(+) channel blockers that were effective inhibitors of PCa cell proliferation. Both hydroxyamides (compounds 1 and 4) and a hydantoin (compound 5) were shown to inhibit the androgen-independent PCa cell line PC-3 in vitro. Electrophysiology showed that all compounds functionally block brain type II voltage-gated Na(+) channels (Nav1.2) expressed in Xenopus laevis oocytes. Long-term growth assays in androgen-independent PC-3 cells showed remarkable inhibition of cell growth, with cells growing to a maximum of 30% of controls with analogue 1. Further, our analogues demonstrated only marginal impact on cell viability over the same treatment interval.