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Protonectin peptides target lipids, act at the interface and selectively kill metastatic breast cancer cells while preserving morphological integrity

2021-05-25Artigo científico Acesso restrito
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dc.contributor.authorBatista Martins, Danubia
dc.contributor.authorFadel, Valmir
dc.contributor.authorOliveira, Filipa D.
dc.contributor.authorGaspar, Diana
dc.contributor.authorAlvares, Dayane S.
dc.contributor.authorCastanho, Miguel A. R. B.
dc.contributor.authorDos Santos Cabrera, Marcia Perez
dc.date.accessioned2021-07-19T12:21:04Z
dc.date.available2021-07-19T12:21:04Z
dc.date.issued2021-05-25
dc.description© 2021 Elsevier Inc. All rights reserved.pt_PT
dc.description.abstractDespite the need for innovative compounds as antimicrobial and anticancer agents, natural sources of peptides remain underexplored. Protonectin (PTN), a cationic dodecapeptide of pharmacological interest, presents large hydrophobicity that is associated with the tendency to aggregate and supposedly influences bioactivity. A disaggregating role was assigned to PTN' N-terminal fragment (PTN1-6), which enhances the bioactivity of PTN in a 1:1 mixture (PTN/PTN1-6). Spectroscopic techniques and model membranes (phospholipid bilayers and SDS micelles) revealed that environment-dependent aggregation is reduced for PTN/PTN1-6, but cytotoxicity of PTNs on MDA-MB-231 breast cancer showed the same CC50 values around 16 µM and on MCF-10A epithelial breast cells 6 to 5-fold higher values, revealing a selective interaction. Since PTN1-6 lacks activity on breast cells, its presence should differently affect PTN activity, suggesting that aggregation could modulate activity depending on the membrane characteristics. Indeed, increased partitioning and lytic activity of PTN/PTN1-6 were found in model membranes independently of charge density, but affected by the curvature tendency. PTN and PTN/PTN1-6 do not alter morphology and roughness of cancer cells, indicating a superficial interaction with membranes and consistent with results obtained in NMR experiments. Our results indicate that aggregation of PTNs depends on the membrane characteristics and modulates the activity of the peptides.pt_PT
dc.description.sponsorshipThis work was supported by the Fundação de Amparo à Pesquisa do Estado de São Paulo – FAPESP [Funding Projects Nos. 2012/24259-0, 2014/08372-7, 2016/50178-8] and Fundação para a Ciência e a Tecnologia, Portugal – FCT I. P. [Funding PTDC/BBB-BQB/1693/2014]. DSA has a postdoctoral fellowship (FAPESP grant# 2015/25620-7) and also thanks CAPES for former scholarships. DBM and FDO acknowledge, respectively, CAPES scholarships and FCT I.P. fellowship [PD/BD/135046/2017]. The Brazilian BioscienceNational Laboratory (LNBio) is acknowledged for the NMR timemachine [proposal RMN-23300].pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationJ Colloid Interface Sci. 2021 May 25;601:517-530pt_PT
dc.identifier.doi10.1016/j.jcis.2021.05.115pt_PT
dc.identifier.eissn1095-7103
dc.identifier.issn0021-9797
dc.identifier.urihttp://hdl.handle.net/10451/48991
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherElsevierpt_PT
dc.relationCell-cell communication in metastatic breast cancer: a control point that can lead to breast cancer treatment
dc.relationExosomes as drug delivery systems in metastatic breast cancer
dc.relation.publisherversionhttps://www.sciencedirect.com/journal/journal-of-colloid-and-interface-sciencept_PT
dc.subjectAFMpt_PT
dc.subjectAggregationpt_PT
dc.subjectAnticancer activitypt_PT
dc.subjectBreast cancer cellspt_PT
dc.subjectModel membranespt_PT
dc.subjectNMR structurept_PT
dc.subjectPeptide-membrane surface interactionpt_PT
dc.subjectProtonectinpt_PT
dc.titleProtonectin peptides target lipids, act at the interface and selectively kill metastatic breast cancer cells while preserving morphological integritypt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleCell-cell communication in metastatic breast cancer: a control point that can lead to breast cancer treatment
oaire.awardTitleExosomes as drug delivery systems in metastatic breast cancer
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FBBB-BQB%2F1693%2F2014/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//PD%2FBD%2F135046%2F2017/PT
oaire.citation.endPage530pt_PT
oaire.citation.startPage517pt_PT
oaire.citation.titleJournal of Colloid and Interface Sciencept_PT
oaire.citation.volume601pt_PT
oaire.fundingStream3599-PPCDT
person.familyNameCastanho
person.givenNameMiguel
person.identifier.orcid0000-0001-7891-7562
person.identifier.scopus-author-id56605575600
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
rcaap.rightsrestrictedAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublicationf5e46f85-fabf-450a-9ee2-1c7b59410892
relation.isAuthorOfPublication.latestForDiscoveryf5e46f85-fabf-450a-9ee2-1c7b59410892
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