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Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

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Trial of the cysteine cathepsin inhibitor JPM-OEt on early and advanced mammary cancer stages in the MMTV-PyMT-transgenic mouse model

Uta Schurigt
  • 1Institut für Molekulare Medizin und Zellforschung, Albert-Ludwigs-Universität Freiburg, D-79104 Freiburg, Germany
/ Lisa Sevenich
  • 2Institut für Molekulare Medizin und Zellforschung, Albert-Ludwigs-Universität Freiburg, D-79104 Freiburg, Germany
/ Corinne Vannier
  • 3Institut für Molekulare Medizin und Zellforschung, Albert-Ludwigs-Universität Freiburg, D-79104 Freiburg, Germany
/ Mieczyslaw Gajda
  • 4Institut für Pathologie, Friedrich-Schiller-Universität Jena, D-07740 Jena, Germany
/ Anne Schwinde
  • 5Institut für Molekulare Medizin und Zellforschung, Albert-Ludwigs-Universität Freiburg, D-79104 Freiburg, Germany
/ Fee Werner
  • 6Institut für Molekulare Medizin und Zellforschung, Albert-Ludwigs-Universität Freiburg, D-79104 Freiburg, Germany
/ Andreas Stahl
  • 7Universitäts-Augenklinik, Albert-Ludwigs-Universität Freiburg, D-79106 Freiburg, Germany
/ Dominik von Elverfeldt
  • 8Abteilung Röntgendiagnostik Medizin Physik, Albert-Ludwigs-Universität Freiburg, D-79106 Freiburg, Germany
/ Anne-Katrin Becker
  • 9Abteilung Röntgendiagnostik Medizin Physik, Albert-Ludwigs-Universität Freiburg, D-79106 Freiburg, Germany
/ Matthew Bogyo
  • 10Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305-5324, USA
/ Christoph Peters
  • 11Institut für Molekulare Medizin und Zellforschung, Albert-Ludwigs-Universität Freiburg, D-79104 Freiburg, Germany
/ Thomas Reinheckel
  • 12Institut für Molekulare Medizin und Zellforschung, Albert-Ludwigs-Universität Freiburg, D-79104 Freiburg, Germany
Published Online: 2008-08-19 | DOI: https://doi.org/10.1515/BC.2008.115


Recent data suggest proteases of the papain-like cysteine cathepsin family as molecular targets for cancer therapy. Here, we report the treatment of polyoma middle T oncogene-induced breast cancers in mice with the cell-permeable broad-spectrum cysteine cathepsin inhibitor JPM-OEt. Up to 100 mg/kg inhibitor was intraperitoneally injected once per day in two trials on early and advanced cancers. In both trials, transient delays in tumour growth were observed. However, at the endpoint of both experiments no significant differences in tumour weights, histopathology and lung metastasis were found between the inhibitor and the control group. The invasive strand formation of collagen I-embedded tumour cell spheroids generated from primary tumours of inhibitor-treated mice in the early cancer trial could be inhibited in vitro by JPM-OEt; a result arguing against induction of resistance to the inhibitor. Measurement of cysteine cathepsin activities in tissue extracts after intraperitoneal injection of JPM-OEt revealed effective inhibition of cysteine cathepsins in pancreas, kidneys and liver, while activities in mammary cancers and in lungs were not significantly affected. We conclude that the pharmacokinetic properties of JPM-OEt, which result in poor bioavailability, may prohibit its use for stand-alone treatment of solid mammary cancers and their lung metastases.

Keywords: pharmacokinetics; protease inhibitor; therapy

Corresponding author

Received: 2007-12-17

Accepted: 2008-03-27

Published Online: 2008-08-19

Published in Print: 2008-08-01

Citation Information: Biological Chemistry. Volume 389, Issue 8, Pages 1067–1074, ISSN (Online) 1437-4315, ISSN (Print) 1431-6730, DOI: https://doi.org/10.1515/BC.2008.115, August 2008

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