A Drosophila model to identify polyamine-drug conjugates that target the polyamine transporter in an intact epithelium

    Authors

    C. Tsen; M. Iltis; N. Kaur; C. Bayer; J. G. Delcros; L. von Kalm;P. Otto

    Comments

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    Abbreviated Journal Title

    J. Med. Chem.

    Keywords

    L1210 LEUKEMIA-CELLS; BIOLOGICAL EVALUATION; MAMMALIAN-CELLS; CHEMOTHERAPEUTIC-AGENTS; MOLECULAR REQUIREMENTS; ANALOG ANTIDIARRHEALS; SELECTIVE DELIVERY; SIGNALING PATHWAY; FLUORESCENT-PROBE; MOSAIC; ANALYSIS; Chemistry, Medicinal

    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 Drosophila-based 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.

    Journal Title

    Journal of Medicinal Chemistry

    Volume

    51

    Issue/Number

    2

    Publication Date

    1-1-2008

    Document Type

    Article

    Language

    English

    First Page

    324

    Last Page

    330

    WOS Identifier

    WOS:000252519600014

    ISSN

    0022-2623

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