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

Biological Chemistry
Andréia GianottiFlávio Henrique-Silva

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.

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Citations

Oct 6, 2010·BMC Structural Biology·Napoleão F ValadaresRichard C Garratt
Nov 19, 2011·Breast Cancer Research : BCR·Bernadette C VictorDora Cavallo-Medved
Apr 8, 2010·Biological Chemistry·Gaetano LetoFrancesca Maria Tumminello
Dec 6, 2012·Genetics and Molecular Research : GMR·A Soares-CostaF Henrique-Silva
Nov 22, 2011·Insect Biochemistry and Molecular Biology·Fernando P P FonsecaFlávio Henrique-Silva
Jan 13, 2016·International Journal of Cancer. Journal International Du Cancer·Dhivya R SudhanDietmar W Siemann
Aug 25, 2015·Pharmacology & Therapeutics·Dhivya R Sudhan, Dietmar W Siemann
Dec 3, 2014·Progress in Neurobiology·Amy M HopkinsDavid L Kaplan
Jun 13, 2017·Journal of Dental Research·A C SantiagoF Henrique-Silva
Sep 30, 2020·Expert Review of Anticancer Therapy·Gaetano Leto, Maria Vittoria Sepporta
Dec 8, 2020·International Journal of Biological Macromolecules·Priscila Yumi Tanaka ShibaoFlavio Henrique-Silva
Jul 31, 2021·Journal of Dental Research·N Da Ponte LeguizamónJ A Cirelli

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