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Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Editorial Board: Buchner, Johannes / Lei, Ming / Ludwig, Stephan / Thomas, Douglas D. / Turk, Boris / Wittinghofer, Alfred


IMPACT FACTOR 2018: 3.014
5-year IMPACT FACTOR: 3.162

CiteScore 2018: 3.09

SCImago Journal Rank (SJR) 2018: 1.482
Source Normalized Impact per Paper (SNIP) 2018: 0.820

Online
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1437-4315
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Volume 389, Issue 4

Issues

Inhibitory effect of the sugarcane cystatin CaneCPI-4 on cathepsins B and L and human breast cancer cell invasion

Andréia Gianotti
  • 1Department of Genetics and Evolution, Federal University of São Carlos, Rodovia Washington Luis km 235, 13565-905, São Carlos, SP, Brazil
  • Other articles by this author:
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/ César A. Sommer
  • 2Department of Genetics and Evolution, Federal University of São Carlos, Rodovia Washington Luis km 235, 13565-905, São Carlos, SP, Brazil
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Adriana K. Carmona
  • 3Department of Biophysics, Federal University of São Paulo, Escola Paulista de Medicina, Rua Três de Maio 100, 04044-020, São Paulo, SP, Brazil
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Flávio Henrique-Silva
  • 4Department of Genetics and Evolution, Federal University of São Carlos, Rodovia Washington Luis km 235, 13565-905, São Carlos, SP, Brazil
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2008-03-27 | DOI: https://doi.org/10.1515/BC.2008.035

Abstract

The lysosomal cysteine proteases cathepsin B and L play important roles in tumor cell invasion. An imbalance between these cathepsins and their endogenous inhibitors, the cystatins, has been associated with development of the metastatic phenotype. Accordingly, many studies have indicated potential use of cystatins in therapeutic approaches. We report a novel cystatin from sugarcane (Saccharum officinarum), CaneCPI-4, with strong inhibitory activity against cathepsins B (K i=0.83 nm) and L (K i=0.021 nm). The invasive ability of MDA-MB-231 human breast cancer cells expressing CaneCPI-4 was only slightly decreased. In contrast, addition of low, non-toxic concentrations of recombinant His-tagged CaneCPI-4 significantly reduced invasion through a Matrigel matrix. Immunoblot analyses failed to detect the recombinant protein inside cells, indicating that the cystatin was not internalized by endocytosis, but exerted its anti-invasive effect mainly through inhibition of extracellular cathepsins. Our findings open the possibility of considering phytocystatins for anti-cancer strategies.

Keywords: cathepsin; cysteine protease inhibitor; Matrigel; phytocystatins; Saccharum officinarum; tumor cell

About the article

Corresponding author


Received: 2007-08-08

Accepted: 2007-12-06

Published Online: 2008-03-27

Published in Print: 2008-04-01


Citation Information: Biological Chemistry, Volume 389, Issue 4, Pages 447–453, ISSN (Online) 14374315, ISSN (Print) 14316730, DOI: https://doi.org/10.1515/BC.2008.035.

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