A Drosophila Model To Identify Polyamine-Drug Conjugates That Target The Polyamine Transporter In An Intact Epithelium

Abstract

Polyamine transport is elevated in many tumor types, suggesting that toxic polyamine - drug conjugates could be targeted to cancer cells via the polyamine transporter (PAT). We have previously reported the use of Chinese hamster ovary (CHO) cells and its PAT-deficient mutant cell line, CHO-MG, to screen anthracene - polyamine conjugates for their PAT-selective targeting ability. We report here a novel Drosophilabased model for screening anthracene-polyamine conjugates in a developing and intact epithelium (Drosophila imaginal discs), wherein cell-cell adhesion properties are maintained. Data from the Drosophila assay are consistent with previous results in CHO cells, indicating that the Drosophila epithelium has a PAT with vertebrate-like characteristics. This assay will be of use to medicinal chemists interested in screening drugs that use PAT for cellular entry, and it offers the possibility of genetic dissection of the polyamine transport process, including identification of a Drosophila PAT. © 2008 American Chemical Society