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dc.contributor.authorEspona Fiedler, Margarita
dc.contributor.authorManuel Manresa, Pilar
dc.contributor.authorBenítez-García, Cristina
dc.contributor.authorFontova Pale, Pere 
dc.contributor.authorQuesada Pato, Roberto 
dc.contributor.authorSoto Cerrato, Vanessa
dc.contributor.authorPérez Tomás, Ricardo
dc.date.accessioned2023-03-20T08:26:03Z
dc.date.available2023-03-20T08:26:03Z
dc.date.issued2022-12
dc.identifier.urihttp://hdl.handle.net/10259/7559
dc.description.abstractMetastasis is the primary cause of death in cancer patients. Many current chemotherapeutic agents only show cytotoxic, but not antimetastatic properties. This leads to a reduction in tumor size, but allows cancer cells to disseminate, which ultimately causes patient death. Therefore, novel anticancer compounds with both effects need to be developed. In this work, we analyze the antimetastatic properties of prodigiosin and obatoclax (GX15-070), anticancer drugs of the Prodiginines (PGs) family. We studied PGs’ effects on cellular adhesion and morphology in the human primary and metastatic melanoma cell lines, SK-MEL-28 and SK-MEL-5, and in the murine melanoma cell line, B16F10A. Cell adhesion sharply decreased in the treated cells, and this was accompanied by a reduction in filopodia protrusions and a significant decrease in the number of focal-adhesion structures. Moreover, cell migration was assessed through the wound-healing assay and cell motility was severely inhibited after 24 h of treatment. To elucidate the molecular mechanisms involved, changes in metastasis-related genes were analyzed through a gene-expression array. Key genes related to cellular invasion, migration and chemoresistance were significantly down-regulated. Finally, an in vivo model of melanoma-induced lung metastasis was established and significant differences in lung tumors were observed in the obatoclax-treated mice. Altogether, these results describe, in depth, PGs’ cellular antimetastatic effects and identify in vivo antimetastatic properties of Obatoclax.en
dc.description.sponsorshipThis research has been funded by Instituto de Salud Carlos III (Grants PI18/00441; FIS PI10/00338) (Co-funded by European Regional Development Fund. ERDF, a way to build Europe).en
dc.format.mimetypeapplication/pdf
dc.language.isoenges
dc.publisherMDPIen
dc.relation.ispartofPharmaceutics. 2022, V. 15, n. 1, 97en
dc.rightsAtribución 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectMetastasisen
dc.subjectObatoclaxen
dc.subjectProdigiosinen
dc.subjectProdigininesen
dc.subjectBH3-mimeticen
dc.subjectMelanomaen
dc.subjectMigrationen
dc.subject.otherQuímica orgánicaes
dc.subject.otherChemistry, Organicen
dc.subject.otherSaludes
dc.subject.otherHealthen
dc.subject.otherMedicinaes
dc.subject.otherMedicineen
dc.titleAntimetastatic Properties of Prodigiosin and the BH3-Mimetic Obatoclax (GX15-070) in Melanomaen
dc.typeinfo:eu-repo/semantics/articlees
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses
dc.relation.publisherversionhttps://doi.org/10.3390/pharmaceutics15010097es
dc.identifier.doi10.3390/pharmaceutics15010097
dc.relation.projectIDinfo:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 (ISCIII)/PI18%2F00441/ES/EVALUACION TERAPEUTICA PRECLINICA EN CANCER DE PULMON DE INHIBIDORES DE SURVIVINA MEDIANTE LA UTILIZACION DE FORMULACIONES NANOENCAPSULADAS Y TERAPIAS COMBINADAS/es
dc.relation.projectIDinfo:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 (ISCIII)/PI10%2F00338/ES/es
dc.identifier.essn1999-4923
dc.journal.titlePharmaceuticsen
dc.volume.number15es
dc.issue.number1es
dc.type.hasVersioninfo:eu-repo/semantics/publishedVersiones


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