Effect of lipidated gonadotropin-releasing hormone peptides on receptor mediated binding and uptake into prostate cancer cells in vitro

Rachel Stephenson; Pegah Varamini; Neville Butcher; Rodney Minchin; Istvan Toth

doi:10.1016/j.nano.2014.06.015

Effect of lipidated gonadotropin-releasing hormone peptides on receptor mediated binding and uptake into prostate cancer cells in vitro

Nanomedicine. 2014 Nov;10(8):1799-808. doi: 10.1016/j.nano.2014.06.015. Epub 2014 Jul 9.

Authors

Rachel Stephenson¹, Pegah Varamini¹, Neville Butcher², Rodney Minchin², Istvan Toth³

Affiliations

¹ School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, QLD, Australia.
² School of Biomedical Sciences, The University of Queensland, St. Lucia, QLD, Australia.
³ School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, QLD, Australia; School of Pharmacy, The University of Queensland, Woollongabba, QLD, Australia. Electronic address: i.toth@uq.edu.au.

PMID: 25014892
DOI: 10.1016/j.nano.2014.06.015

Abstract

Gonadotropin-releasing hormone (GnRH) receptors are overexpressed on many cancer cells but not on primary cell lines. This study was designed to investigate the targeting ability and uptake of dendritic lipidated [Gln(1)]-GnRH peptide analogues on receptor-positive prostate cancer PC-3 cells relative to receptor-negative ovarian carcinoma SKOV-3 cells for potential application in drug delivery. Direct antiproliferative effect of these was investigated on three GnRH-receptor positive cancer cells, PC-3, LNCaP and DU145. A significant dose dependent growth inhibitory effect was produced in DU145 cells by 5 dendrimers giving an IC50 value of 22-35 μM. All compounds were non-toxic to the normal peripheral blood mononuclear cells.

From the clinical editor: This study demonstrates the use of specific dendritic lapidated GnRH analogues in growth inhibition of GnRH receptor positive prostate cancer cell lines, suggesting potential future clinical use of this or similar strategies to address GnRH receptor positive cancer cells.

Keywords: Gonadotropin-releasing hormone; Lipoamino acid; Prostate cancer; Solid phase peptide synthesis; Targeting.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Line, Tumor
Gonadotropin-Releasing Hormone / chemistry*
Humans
Male
Peptides / chemistry*
Peptides / metabolism*
Receptors, LHRH / metabolism*

Substances

Peptides
Receptors, LHRH
Gonadotropin-Releasing Hormone