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

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dc.contributorLETA - Laboratório de Toxinologia Aplicadapt_BR
dc.contributorCentro de Toxinas, Resposta-imune e Sinalização Celular (CeTICS)pt_BR
dc.contributorLab. Imunoquímicapt_BR
dc.contributor.authorFerreira, Adilson Kleberpt_BR
dc.contributor.authorCristofaro, Brunellapt_BR
dc.contributor.authorMenezes, Milene Cristinapt_BR
dc.contributor.authorOliveira, Ana Karina dept_BR
dc.contributor.authorTashima, Alexandre Keijipt_BR
dc.contributor.authorMelo, Robson Lopes dept_BR
dc.contributor.authorSilva, Cristiane Castilho Fernandes dapt_BR
dc.contributor.authorRodriguez, Miryam Guillermina Palominopt_BR
dc.contributor.authorCajado-Carvalho, Danielapt_BR
dc.contributor.authorAzevedo, Ricardo Alexandre dept_BR
dc.contributor.authorSá Junior, Paulo Luiz dept_BR
dc.contributor.authorMambelli, Lisley Inatapt_BR
dc.contributor.authorPortaro, Fernanda Calheta Vieirapt_BR
dc.contributor.authorPardanaud, Lucpt_BR
dc.contributor.authorEichmann, Annept_BR
dc.contributor.authorSant'anna, Osvaldo Augustopt_BR
dc.contributor.authorFaria, Marcellapt_BR
dc.date.accessioned2021-01-21T18:32:53Z-
dc.date.available2021-01-21T18:32:53Z-
dc.date.issued2020pt_BR
dc.identifier.citationFerreira AK, Cristofaro B, Menezes MC, Oliveira AK, Tashima AK, Melo RL, et al. 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. Oncotarget. 2020 Dec;11(51):4770-4787. doi:10.18632/oncotarget.27839.pt_BR
dc.identifier.urihttps://repositorio.butantan.gov.br/handle/butantan/3473-
dc.description.abstractMost 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.pt_BR
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)pt_BR
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)pt_BR
dc.format.extent4770-4787pt_BR
dc.language.isoEnglishpt_BR
dc.relation.ispartofOncotargetpt_BR
dc.rightsOpen Accesspt_BR
dc.titleAlphastatin-C a new inhibitor of endothelial cell activation is a pro-arteriogenic agent in vivo and retards B16-F10 melanoma growth in a preclinical modelpt_BR
dc.typeArticlept_BR
dc.identifier.doi10.18632/oncotarget.27839pt_BR
dc.identifier.urlhttps://doi.org/10.18632/oncotarget.27839pt_BR
dc.contributor.externalUniversidade de São Paulo (USP)pt_BR
dc.contributor.externalYale Universitypt_BR
dc.contributor.externalParis-Cardiovascular Research Center (PARCC)pt_BR
dc.contributor.externalUniversidade de Mogi das Cruzes (UMC)pt_BR
dc.contributor.externalCollège de Francept_BR
dc.contributor.externalUniversidade Federal de São Paulo (UNIFESP)pt_BR
dc.identifier.citationvolume11pt_BR
dc.identifier.citationissue51pt_BR
dc.subject.keywordalphastatin-Cpt_BR
dc.subject.keywordangiogenesispt_BR
dc.subject.keywordpeptidespt_BR
dc.subject.keywordmelanomapt_BR
dc.subject.keywordangiostaticpt_BR
dc.relation.ispartofabbreviatedOncotargetpt_BR
dc.identifier.citationabntv. 11, n. 51, p. 4770-4787, dez. 2020pt_BR
dc.identifier.citationvancouver2020 Dec;11(51):4770-4787pt_BR
dc.contributor.butantanMenezes, Milene Cristina|:Aluno|:Laboratório Especial de Toxinologia Aplicada (LETA):Centro de Toxinas, Resposta-imune e Sinalização Celular (CeTICS)pt_BR
dc.contributor.butantanOliveira, Ana Karina de|:Aluno|:Laboratório Especial de Toxinologia Aplicada (LETA):Centro de Toxinas, Resposta-imune e Sinalização Celular (CeTICS)pt_BR
dc.contributor.butantanTashima, Alexandre Keiji|:Aluno|:Laboratório Especial de Toxinologia Aplicada (LETA)|:Centro de Toxinas, Resposta-imune e Sinalização Celular (CeTICS)pt_BR
dc.contributor.butantanMelo, Robson Lopes de|:Colaborador|:Laboratório Especial de Toxinologia Aplicada (LETA)|:Centro de Toxinas, Resposta-imune e Sinalização Celular (CeTICS)pt_BR
dc.contributor.butantanSilva, Cristiane Castilho Fernandes da|:Aluno|:Lab. Imunoquímicapt_BR
dc.contributor.butantanRodriguez, Miryam Guillermina Palomino|:Aluno|:Laboratório Especial de Toxinologia Aplicada (LETA)|:Centro de Toxinas, Resposta-imune e Sinalização Celular (CeTICS)pt_BR
dc.contributor.butantanCajado-Carvalho, Daniela|:Aluno|:Lab. Imunoquímicapt_BR
dc.contributor.butantanPortaro, Fernanda Calheta Vieira|:Pesquisador:Docente Permanente PPGTOX|:Lab. Imunoquímicapt_BR
dc.contributor.butantanSant'anna, Osvaldo Augusto|:Pesquisador|:Lab. Imunoquímicapt_BR
dc.contributor.butantanFaria, Marcella|:Colaborador|:Laboratório Especial de Toxinologia Aplicada (LETA)|:Centro de Toxinas, Resposta-imune e Sinalização Celular (CeTICS)pt_BR
dc.sponsorship.butantanFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)¦¦2008/54192-0pt_BR
dc.sponsorship.butantanFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)¦¦2015/18528-7pt_BR
dc.sponsorship.butantanFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)¦¦2013/07273-2pt_BR
dc.sponsorship.butantanConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)¦¦304255/2017-3pt_BR
dc.identifier.bvsccBR78.1pt_BR
dc.identifier.bvsdbIBProdpt_BR
dc.description.dbindexedYespt_BR
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