Alphastatin-C a new inhibitor of endothelial cell activation is a pro-arteriogenic agent in vivo and retards B16-F10 melanoma growth in a preclinical model
Year: 2020
Type: article
Abstract: // Adilson Kleber Ferreira 2 , 3 , Brunella Cristofaro 8 , Milene Cristina Menezes 1 , Ana Karina de Oliveira 1 , Alexandre Keiji Tashima 1 , 9 , Robson Lopes de Melo 1 , Cristiane Castilho Fernandes Silva 4 , Miryam Guillermina Palomino Rodriguez 1 , Daniela Cajado de Oliveira Souza Carvalho 4 , Ricardo Alexandre de Azevedo 10 , Paulo Luiz de Sá Junior 7 , Lisley Inata Mambelli 2 , Fernanda Vieira Portaro 4 , Luc Pardanaud 5 , 6 , Anne Eichmann 5 , 6 , Osvaldo Augusto Sant’Anna 1 and Mxarcella Faria 1 1 Special Laboratory of Applied Toxinology, Center of Toxins, Immune-Response and Cell Signaling (CeTICS), Butantan Institute, São Paulo, SP, Brazil 2 Department of Immunology, Laboratory of Tumor Immunology, Institute of Biomedical Science, University of Sao Paulo, Sao Paulo, SP, Brazil 3 Alchemypet, Veterinary Dignostic Medicine, CIETEC/IPEN, Department of Oncology, University of Sao Paulo, Sao Paulo, Brazil 4 Immunochemistry Laboratory, Butantan Institute, São Paulo, SP, Brazil 5 Cardiovascular Research Center and the Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, CT, USA 6 INSERM U970, Paris Cardiovascular Research Center, Paris, France 7 Mogi das Cruzes University (UMC), Villa Lobos Campus, Sao Paulo, SP, Brazil 8 Center for Interdisciplinary Research in Biology (CIRB), Collège de France, Paris, France 9 Department of Biochemistry, Escola Paulista de Medicina, Federal University of Sao Paulo, Sao Paulo, Brazil 10 Experimental Oncology Unit (UNONEX), Federal University of Sao Paulo, Sao Paulo, SP, Brazil Correspondence to: Marcella Faria, email: [email protected] Adilson Kleber Ferreira, email: [email protected] Keywords: alphastatin-C; angiogenesis; peptides; melanoma; angiostatic Received: December 22, 2017 Accepted: June 23, 2018 Published: December 22, 2020 Copyright: © 2020 Ferreira et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ABSTRACT Most characterized angiogenic modulators are proteolytic fragments of structural plasma and/or matrix components. Herein, we have identified a novel anti-angiogenic peptide generated by the in vitro hydrolysis of the C-terminal moiety of the fibrinogen alpha chain, produced by the snake venom metalloprotease bothropasin (SVMP), a hemorrhagic proteinase in Bothrops jararaca venom. The 14-amino acids peptide (alphastatin-C) is a potent antagonist of basic fibroblast growth factor, induced endothelial cell (HUVEC-CS) proliferation, migration and capillary tube formation in matrigel. It also inhibits cell adhesion to fibronectin. The basis of the antagonism between bFGF and alphastatin-C is elucidated by the inhibition of various bFGF induced signaling pathways and their molecular components modification, whenever the combination of the stimuli is provided, in comparison to the treatment with bFGF only. To corroborate to the potential therapeutic use of alphastatin-C, we have chosen to perform in vivo assays in two distinct angiogenic settings. In chick model, alphastatin-C inhibits chorioallantoic membrane angiogenesis. In mouse, it efficiently reduces tumor number and volume in a melanoma model, due to the impairment of tumor neovascularization in treated mice. In contrast, we show that the alphastatin-C peptide induces arteriogenesis, increasing pial collateral density in neonate mice. alphastatin-C is an efficient new antiangiogenic FGF-associated agent in vitro , it is an inhibitor of embryonic and tumor vascularization in vivo while, it is an arteriogenic agent. The results also suggest that SVMPs can be used as in vitro biochemical tools to process plasma and/or matrix macromolecular components unraveling new angiostatic peptides.
Source: Oncotarget
Authors: Adilson Kleber Ferreira, Brunella Cristofaro, Milene Cristina Menezes, Ana Karina de Oliveira, Alexandre Keiji Tashima, Robson Lopes de Melo, Cristiane Castilho Fernandes Silva, Miryam Guillermina Palomino Rodriguez, Daniela Cajado de Oliveira Souza Carvalho, Ricardo Alexandre de Azevedo, Paulo Luiz de Sá Junior, Lisley Inata Mambelli, Fernanda Vieira Portaro, Luc Pardanaud, Anne Eichmann, Osvaldo Augusto Sant’Anna, Mxarcella Faria
Institutions: Universidade de São Paulo, Centro de Inovação, Empreendedorismo e Tecnologia, Collège de France, Centre Interdisciplinaire de Recherche en Biologie, Instituto Butantan, Universidade Federal de São Paulo, Universidade de Mogi das Cruzes, Inserm, Yale University, Paris Cardiovascular Research Center
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: diamond
Awards: G2297171240, Rational design and development of new prototypes derived of antitumor phospholipids as potential inhibitors of the enzyme CtP: phosphoethanolamine citidililtransferase and antitumor agents in non-small cell lung cancer, Caracterização de polipeptídeos moduladores de angiogênese derivados: de degradação de componentes da membrana basal por enzimas proteolíticas do veneno de serpentes; da fração peptídica dos venenos de serpentes, G4402799499, G6626691390, Development of new drug candidate for the treatment of non-small cell lung cancer: CHY-1 as a novel inhibitor of autophagy and prototype of a novel class of inhibitors of the enzyme CTP: phosphoethanolamine citidililtransferase
OpenAlex ID: W3115854638