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Antimigratory and antiproliferative effects of the brain‐targeted peptide conjugate PepH3‐vCPP2319 on triple negative breast cancer cell cultures

2025Journal article Restricted access
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dc.contributor.authorGonçalves, Catarina
dc.contributor.authorCastanho, Miguel A. R. B.
dc.contributor.authorCavaco, Marco
dc.contributor.authorNeves, Vera
dc.date.accessioned2025-07-02T13:28:10Z
dc.date.available2025-07-02T13:28:10Z
dc.date.issued2025
dc.description© 2025 European Peptide Society and John Wiley & Sons, Ltd.pt_PT
dc.description.abstractTriple-negative breast cancer (TNBC) is an aggressive breast cancer subtype affecting mostly younger women with a poor 5-year overall survival. It is characterized by a high metastization rate, particularly to the brain, where the blood-brain barrier (BBB) hinders the pharmaceuticals delivery. New anticancer drugs able to inhibit cell migration are required to effectively prevent the development of metastasis. PepH3-vCPP2319 (AGILKRW(Ahx)WRRRYRRWRRRRRQRRRPRR-amide), consisting of the conjugation of the BBB peptide shuttle (BBBpS) PepH3 (AGILKRW-amide) to the anticancer peptide (ACP) vCPP2319 (WRRRYRRWRRRRRQRRRPRR-amide), was reported to have high anticancer activity (IC50 = 5.0 μM) toward highly aggressive TNBC cells (MDA-MB-231) paired with 2-fold increased accumulation in the brain when compared to unconjugated vCPP2319. Herein, we demonstrate that PepH3-vCPP2319 inhibits cell migration and proliferation in wound healing assays, outperforming the gold standard small chemical inhibitor, iCRT-3. The concentration required to inhibit cell migration is 10-fold lower for PepH3-vCPP2319 (0.5 μM) when compared with iCRT-3 (50 μM). Likewise, PepH3-vCPP2319 at 2.5 μM was more efficient in preventing cell proliferation when compared with 50 μM iCRT-3, with 45% reduction in spheroid diameter. This study sheds light on the antimetastatic potential of PepH3-vCPP2319 through abrogation of cell migration to distant sites, including the brain.pt_PT
dc.description.sponsorshipThe project leading to these results has received funding from “la Caixa” Foundation (ID 100010434) and FCT, I. P under the agreement LCF/ PR/HP21/52310015 and “Fundação para a Ciência e Tecnologia” (FCT, Portugal) (grant: 2021.00895.CEECIND, PD/BD/128281/2017, PTDC/QUI- OUT/3854/2021; 2023.12099.PEX). We also acknowledge FCT for the PhD scholarship—UI/BD/151171/2021pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationJ Pept Sci. 2025 Aug;31(8):e70035pt_PT
dc.identifier.doi10.1002/psc.70035pt_PT
dc.identifier.eissn1099-1387
dc.identifier.issn1075-2617
dc.identifier.urihttp://hdl.handle.net/10400.5/101973
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherWileypt_PT
dc.relationLCF/PR/HP21/52310015pt_PT
dc.relationDiagnostic tool for Alzheimer’s disease based on a proprietary blood-brain barrier peptide shuttle-nanoparticle
dc.relationPPBI-POCI-01-0145-FEDER-022122pt_PT
dc.relation.publisherversionhttps://onlinelibrary.wiley.com/journal/10991387pt_PT
dc.subjectAnticancer peptidespt_PT
dc.subjectCancer metastasispt_PT
dc.subjectCancer stem cellspt_PT
dc.subjectCell migrationpt_PT
dc.subjectTriple negative breast cancerpt_PT
dc.titleAntimigratory and antiproliferative effects of the brain‐targeted peptide conjugate PepH3‐vCPP2319 on triple negative breast cancer cell culturespt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleDiagnostic tool for Alzheimer’s disease based on a proprietary blood-brain barrier peptide shuttle-nanoparticle
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/CEEC IND4ed/2021.00895.CEECIND%2FCP1673%2FCT0004/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/OE/PD%2FBD%2F128281%2F2017/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FQUI-OUT%2F3854%2F2021/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/Concurso de Projetos Exploratórios em Todos os Domínios Científicos 2023/2023.12099.PEX/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//UI%2FBD%2F151171%2F2021/PT
oaire.citation.issue8pt_PT
oaire.citation.titleJournal of Peptide Sciencept_PT
oaire.citation.volume31pt_PT
oaire.fundingStreamCEEC IND4ed
oaire.fundingStreamOE
oaire.fundingStream3599-PPCDT
oaire.fundingStreamConcurso de Projetos Exploratórios em Todos os Domínios Científicos 2023
person.familyNameCastanho
person.familyNameCavaco
person.familyNameNeves
person.givenNameMiguel
person.givenNameMarco
person.givenNameVera
person.identifier1069324
person.identifier953259
person.identifier.ciencia-id1412-63B8-7494
person.identifier.ciencia-id671C-1860-A160
person.identifier.orcid0000-0001-7891-7562
person.identifier.orcid0000-0002-0938-9038
person.identifier.orcid0000-0002-2989-7208
person.identifier.ridO-2176-2018
person.identifier.scopus-author-id56605575600
person.identifier.scopus-author-id26537945300
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsrestrictedAccesspt_PT
rcaap.typearticlept_PT
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