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Inhibition of ‘in vitro’ tumor cell growth by aromatic polyamidines exhibiting antiproteinase activity

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Abstract

Aromatic polyamidines containing two, three or four benzamidine residues inhibit proteinase activity and proliferation of different human tumor cell lines, including leukemic (K562, HEL), melanoma (Colo 38) and B-lymphoid (WI-L2) cell lines. In addition, the benzamidine derivatives analysed in the present study inhibit cell growth of the Chinese hamster FHO6T1-1 cell line, obtained after transfection of primary lung cells with the activated human T24-Ha-ras-1 oncogene.

After treatment of FHO6T1-1 cells with benzamidine derivatives, a sharp decrease of the content of Ha-ras-1 mRNA was found, but not of transferrin receptor mRNA.

We found that inhibition of cell proliferation by tetra-benzamidine derivatives is not restricted to tumor cells, but concerns also non-tumorigenic cell lines as well as normal primary fibroblasts. Therefore, our analysis was extended to di- and tri-benzamidine derivatives, which could be proposed as useful substrates in the synthesis of drug-conjugated monoclonal antibodies or growth factors. The data obtained demonstrate that these latter compounds and their halo-derivatives also exhibit strong antiproliferative effects onin vitro cultured cells.

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Authors and Affiliations

  1. Dipartimento di Scienze Farmaceutiche, Università di Ferrara, Via Scandiana 21, Ferrara, Italy

    Claudio Nastruzzi, Roberto Ferroni & Mario Guarneri

  2. Istituto di Chimica Biologica, Università di Ferrara, Via L. Borsari n. 46, 44100, Ferrara, Italy

    Giordana Feriotto, Rafaella Barbieri & Roberto Gambari

  3. Garscube Estate, Beatson Institute for Cancer Research, Switchback Road, G61 1BD, Bearsden, Glasgow, Scotland, UK

    Demetrios Spandidos

  4. Hellenic Institute Pasteur, 127 Vas. Sofias Ave, Athens, Greece

    Demetrios Spandidos

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  1. Claudio Nastruzzi
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  2. Giordana Feriotto
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  3. Demetrios Spandidos
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  4. Roberto Ferroni
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  5. Mario Guarneri
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  6. Rafaella Barbieri
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  7. Roberto Gambari
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Nastruzzi, C., Feriotto, G., Spandidos, D. et al. Inhibition of ‘in vitro’ tumor cell growth by aromatic polyamidines exhibiting antiproteinase activity. Clin Exp Metast 7, 25–39 (1989). https://doi.org/10.1007/BF02057179

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  • DOI: https://doi.org/10.1007/BF02057179

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