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In vitro and in vivo anticancer effects of two quinoline-platinum(II) complexes on human osteosarcoma models

2019-04Journal article Restricted access
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dc.contributor.authorCarolina Ruiz, Maria
dc.contributor.authorResasco, Agustina
dc.contributor.authorLaura Di Virgilio, Ana
dc.contributor.authorAyala, Miguel
dc.contributor.authorCavaco, Isabel
dc.contributor.authorCabrera, Silvia
dc.contributor.authorAleman, Jose
dc.contributor.authorEsteban Leon, Ignacio
dc.date.accessioned2020-07-24T10:52:36Z
dc.date.available2020-07-24T10:52:36Z
dc.date.issued2019-04
dc.description.abstractPlatinum-based drugs, mainly cisplatin, are used for the treatment of several solid tumors such as OS. However, cisplatin treatment often results in the development of chemoresistance, leading therapeutic failure. We have previously reported that platinum complexes containing 8-hydroxyquinoline ligands have good antitumor activity against different cancer cell lines and with a different and better cytotoxic profile than cisplatin. Here, the anticancer properties of two different quinoline-platinum complexes [Pt(Cl)(2)(quinoline)(dmso)] (1) [PtCl(8-O-quinoline)(dmso)] (2) on in vitro (2D and 3D) and in vivo models (xenograft tumor of human osteosarcoma in mice) are presented. In this order, [PtCl(8-O-quinoline)(dmso)] (2) impaired cell viability to have a more pronounced antitumor effect than cisplatin on MG-63 osteosarcoma cells (IC50 4 mu M vs. 39 mu M). Besides, [PtCl(8-O-quinoline)(dmso)] (2) increased ROS production in a dose-manner response and this compound induced early and late apoptotic fractions of human osteosarcoma cells. Finally, [PtCl(8-O-quinoline)(dmso)] (2) decreased the cell viability of multicellular spheroids and reduced the tumor volume on athymic nude mice N:NIH(S) Fox1(nu) without inducing side effects. In this way, [PtCl(8-O-quinoline)(dmso)] (2) did not alter the normal cytoarchitecture of liver and kidney and the blood biomarkers (GPT, GOT, uremia, and creatinine) did not suffer modifications. Taken together, our data indicate that these compounds showed a better anticancer performance than cisplatin on in vitro and in vivo studies. These results showed the importance of chelation in the antitumor properties, suggesting that the [PtCl(8-O-quinoline)(dmso)] (2) might be a promising agent for the treatment of human osteosarcoma tumors resistant to cisplatin.
dc.description.sponsorshipUNLPNational University of La Plata [11X/690]
dc.description.sponsorshipCONICETConsejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET) [PIP 00340]
dc.description.sponsorshipANPCyTANPCyT [PICT 2014-2223, CTQ2015-64561-R]
dc.description.versioninfo:eu-repo/semantics/publishedVersion
dc.identifier.doi10.1007/s00280-019-03773-x
dc.identifier.issn0344-5704
dc.identifier.issn1432-0843
dc.identifier.urihttp://hdl.handle.net/10400.1/14382
dc.language.isoeng
dc.peerreviewedyes
dc.publisherSpringer
dc.subjectPlatinum complexes
dc.subjectCell-cycle
dc.subjectTumor
dc.subjectDrug
dc.subjectStress
dc.subjectAssay
dc.subjectProliferation
dc.subjectResistance
dc.subjectToxicity
dc.subjectChrysin
dc.titleIn vitro and in vivo anticancer effects of two quinoline-platinum(II) complexes on human osteosarcoma models
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage692
oaire.citation.issue4
oaire.citation.startPage681
oaire.citation.titleCancer Chemotherapy and Pharmacology
oaire.citation.volume83
person.familyNamePALMA ANTUNES CAVACO
person.givenNameISABEL MARIA
person.identifierH-9087-2012
person.identifier.ciencia-idD515-FB5E-1205
person.identifier.orcid0000-0001-8651-9054
rcaap.rightsrestrictedAccess
rcaap.typearticle
relation.isAuthorOfPublicationb499959b-bea5-4292-bdb2-4311b0aa82de
relation.isAuthorOfPublication.latestForDiscoveryb499959b-bea5-4292-bdb2-4311b0aa82de

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