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Title: Inhibitory effect of the sugarcane cystatin CaneCPI-4 on cathepsins B and L and human breast cancer cell invasion
Authors: Gianotti, Andreia
Sommer, Csar A.
Carmona, Adriana K. [UNIFESP]
Henrique-Silva, Flavio
Universidade Federal de São Carlos (UFSCar)
Universidade Federal de São Paulo (UNIFESP)
Keywords: cathepsin
cysteine protease inhibitor
Saccharurn officinarum
tumor cell
Issue Date: 1-Apr-2008
Publisher: Walter de Gruyter & Co
Citation: Biological Chemistry. Berlin: Walter de Gruyter & Co, v. 389, n. 4, p. 447-453, 2008.
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.
ISSN: 1431-6730
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