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Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Editorial Board Member: Buchner, Johannes / Ludwig, Stephan / Sies, Helmut / Turk, Boris / Wittinghofer, Alfred

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The effects of a plant proteinase inhibitor from Enterolobium contortisiliquum on human tumor cell lines

Adriana Miti Nakahata1, a / Barbara Mayer2, a / Christian Ries3 / Cláudia Alessandra Andrade de Paula1 / Marisa Karow3 / Peter Neth3 / Misako U. Sampaio1 / Marianne Jochum3 / 1

1Departamento de Bioquímica, Universidade Federal de São Paulo-Escola Paulista de Medicina, Rua Três de Maio 100, 04044-020, São Paulo, SP, Brazil

2Department of Surgery, Clinic Großhadern, Ludwig Maximilians University Munich, D-81377 Munich, Germany

3Division of Clinical Chemistry and Clinical Biochemistry, Ludwig Maximilians University Munich, D-80366 Munich, Germany

aThese authors contributed equally to this work.

Corresponding author

Citation Information: Biological Chemistry. Volume 392, Issue 4, Pages 327–336, ISSN (Online) 1437-4315, ISSN (Print) 1431-6730, DOI: 10.1515/bc.2011.031, July 2011

Publication History

Received:
2010-07-27
Accepted:
2010-10-27
Published Online:
2011-07-25

Abstract

Supplementary to the efficient inhibition of trypsin, chymotrypsin, plasma kallikrein, and plasmin already described by the EcTI inhibitor from Enterolobium contortisiliquum, it also blocks human neutrophil elastase (K iapp=4.3 nm) and prevents phorbol ester (PMA)-stimulated activation of matrix metalloproteinase (MMP)-2 probably via interference with membrane-type 1 (MT1)-MMP. Moreover, plasminogen-induced activation of proMMP-9 and processing of active MMP-2 was also inhibited. Furthermore, the effect of EcTI on the human cancer cell lines HCT116 and HT29 (colorectal), SkBr-3 and MCF-7 (breast), K562 and THP-1 (leukemia), as well as on human primary fibroblasts and human mesenchymal stem cells (hMSCs) was studied. EcTI inhibited in a concentration range of 1.0–2.5 μm rather specifically tumor cell viability without targeting primary fibroblasts and hMSCs. Taken together, our data indicate that the polyspecific proteinase inhibitor EcTI prevents proMMP activation and is cytotoxic against tumor cells without affecting normal tissue remodeling fibroblasts or regenerative hMSCs being an important tool in the studies of tumor cell development and dissemination.

Keywords: cancer; Kunitz inhibitors; matrix metalloproteinases; mesenchymal stem cells; plant proteinases

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