Inhibitory effect of the sugarcane cystatin CaneCPI-4 on cathepsins B and L and human breast cancer cell invasion
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Andréia Gianotti
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 (Ki=0.83 nm) and L (Ki=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.
©2008 by Walter de Gruyter Berlin New York
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- Role of histone modifications in defining chromatin structure and function
- Differential loss of histone H3 isoforms mono-, di- and tri-methylated at lysine 4 during X-inactivation in female embryonic stem cells
- Disentanglement of protease substrate repertoires
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Articles in the same Issue
- Highlight: 59th Mosbach Kolloquium
- The role of long non-coding RNAs in chromatin structure and gene regulation: variations on a theme
- The histone H1 family: specific members, specific functions?
- ATP-dependent chromatosome remodeling
- Role of histone modifications in defining chromatin structure and function
- Differential loss of histone H3 isoforms mono-, di- and tri-methylated at lysine 4 during X-inactivation in female embryonic stem cells
- Disentanglement of protease substrate repertoires
- p53-dependent repression of the human MCL-1 gene encoding an anti-apoptotic member of the BCL-2 family: the role of Sp1 and of basic transcription factor binding sites in the MCL-1 promoter
- 5′-End maturation of tRNA in Aquifex aeolicus
- Smurf1 directly targets hPEM-2, a GEF for Cdc42, via a novel combination of protein interaction modules in the ubiquitin-proteasome pathway
- Purification and characterization of natural Ara h 8, the Bet v 1 homologous allergen from peanut, provides a novel isoform
- Human butyrylcholinesterase components differ in aryl acylamidase activity
- Ribosome display and selection of human anti-CD22 scFvs derived from an acute lymphocytic leukemia patient
- Sub-chronic administration of the 11β-HSD1 inhibitor, carbenoxolone, improves glucose tolerance and insulin sensitivity in mice with diet-induced obesity
- Inhibitory effect of the sugarcane cystatin CaneCPI-4 on cathepsins B and L and human breast cancer cell invasion
