This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Anderson, J. D. Articles by Brown, M. L. Search for Related Content PubMed PubMed Citation Articles by Anderson, J. D. Articles by Brown, M. L.

¹ Departments of Chemistry and ² Anesthesiology, University of Virginia, Charlottesville, VA, and ³ Department of Biological Sciences, University of Delaware, Newark, DE

Requests for Reprints:Milton L. Brown, Department of Chemistry, University of Virginia, McCormick Road, P. O. Box 400319, Charlottesville, VA 22904. Phone: (434) 982-3091; Fax: (434) 924-0798. E-mail: mlb2v{at}virginia.edu

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.

Grant support:Jeffress Trust (M. L. B.), Paul Mellon Fund (M. L. B.), and University of Virginia Burger Center for Biological Sciences (M. L. B.). Additional funding from University of Delaware Research Foundation (R. A. S.) and Department of Biological Sciences, University of Delaware (R. A. S.).

Received 1/ 8/03; revised 8/19/03; accepted 8/28/03.

This article has been cited by other articles:

				W. J. Brackenbury and M. B. A. Djamgoz Activity-dependent regulation of voltage-gated Na+ channel expression in Mat-LyLu rat prostate cancer cell line J. Physiol., June 1, 2006; 573(2): 343 - 356. [Abstract] [Full Text] [PDF]