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Cytotoxic mechanism of sphaerodactylomelol, an uncommon bromoditerpene isolated from sphaerococcus coronopifolius

2021Journal article Open access
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dc.contributor.authorAlves, Celso
dc.contributor.authorSilva, Joana
dc.contributor.authorPinteus, Susete
dc.contributor.authorAlonso, Eva
dc.contributor.authorAlvarino, Rebeca
dc.contributor.authorDuarte, Adriana
dc.contributor.authorMarmitt, Diorge
dc.contributor.authorGeottert, Márcia Inês
dc.contributor.authorGaspar, Helena
dc.contributor.authorAlfonso, Amparo
dc.contributor.authorAlpoim, Maria C.
dc.contributor.authorBotana, Luis M
dc.contributor.authorPedrosa, Rui
dc.date.accessioned2021-07-29T10:29:33Z
dc.date.available2021-07-29T10:29:33Z
dc.date.issued2021
dc.descriptionThis work was supported by the Portuguese Foundation for Science and Technology (FCT) through the strategic project UID/MAR/04292/2020 to MARE—Marine and Environmental Sciences Centre and UIDP/Multi/04046/2020 and UIDB/04046/2020 granted to BioISI—BioSystems and Integrative Sciences Institute, through POINT4PAC project (Oncologia de Precisão: Terapias e Tecnologias Inovadoras (SAICTPAC/0019/ 2015-LISBOA- 01-0145-FEDER-016405), through CROSS-ATLANTIC project (PTDC/BIA-OUT/29250/2017), co-financed by COMPETE (POCI-01-0145-FEDER-029250). FCT is also acknowledged for the grant attributed to J.S. (SFRH/BD/103255/2014).
dc.description.abstractMarine natural products have exhibited uncommon chemical structures with relevant antitumor properties highlighting their potential to inspire the development of new anticancer agents. The goal of this work was to study the antitumor activities of the brominated diterpene sphaerodactylomelol, a rare example of the dactylomelane family. Cytotoxicity (10–100 M; 24 h) was evaluated on tumor cells (A549, CACO-2, HCT-15, MCF-7, NCI-H226, PC-3, SH-SY5Y, SK-ML-28) and the effects estimated by MTT assay. Hydrogen peroxide (H2O2) levels and apoptosis biomarkers (membrane translocation of phosphatidylserine, depolarization of mitochondrial membrane potential, Caspase-9 activity, and DNA condensation and/or fragmentation) were studied in the breast adenocarcinoma cellular model (MCF-7) and its genotoxicity on mouse fibroblasts (L929). Sphaerodactylomelol displayed an IC50 range between 33.04 and 89.41 M without selective activity for a specific tumor tissue. The cells’ viability decrease was accompanied by an increase on H2O2 production, a depolarization of mitochondrial membrane potential and an increase of Caspase-9 activity and DNA fragmentation. However, the DNA damage studies in L929 non-malignant cell line suggested that this compound is not genotoxic for normal fibroblasts. Overall, the results suggest that the cytotoxicity of sphaerodactylomelol seems to be mediated by an increase of H2O2 levels and downstream apoptosis.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationAlves, C.; Silva, J.; Pinteus, S.; Alonso, E.; Alvariño, R.; Duarte, A.; Marmitt, D.; Goettert, M.I.; Gaspar, H.; Alfonso, A.; et al. Cytotoxic Mechanism of Sphaerodactylomelol, an Uncommon Bromoditerpene Isolated from Sphaerococcus coronopifolius. Molecules 2021, 26, 1374. https://doi.org/ 10.3390/molecules26051374pt_PT
dc.identifier.doi10.3390/molecules26051374pt_PT
dc.identifier.issn1420-3049
dc.identifier.urihttp://hdl.handle.net/10400.8/5960
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherMDPIpt_PT
dc.relationPRECISION ONCOLOGY BY INNOVATIVE THERAPIES AND TECHNOLOGIES
dc.relationNeuroprotective effects of molecules isolated from Bifurcaria bifurcata and Codium tomentosum in an in vitro and in vivo Parkinson Disease model.
dc.relation.publisherversionhttps://www.mdpi.com/1420-3049/26/5/1374/htmpt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectBreast cancerpt_PT
dc.subjectRed algaept_PT
dc.subjectOxidative stresspt_PT
dc.subjectMarine natural productspt_PT
dc.subjectApoptosispt_PT
dc.subjectDNA damagept_PT
dc.subjectBiological activitiespt_PT
dc.subjectMCF-7 cellspt_PT
dc.titleCytotoxic mechanism of sphaerodactylomelol, an uncommon bromoditerpene isolated from sphaerococcus coronopifoliuspt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitlePRECISION ONCOLOGY BY INNOVATIVE THERAPIES AND TECHNOLOGIES
oaire.awardTitleNeuroprotective effects of molecules isolated from Bifurcaria bifurcata and Codium tomentosum in an in vitro and in vivo Parkinson Disease model.
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/9471 - RIDTI/SAICTPAC%2F0019%2F2015/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/9471 - RIDTI/PTDC%2FBIA-OUT%2F29250%2F2017/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/POR_CENTRO/SFRH%2FBD%2F103255%2F2014/PT
oaire.citation.titleMoleculespt_PT
oaire.citation.volume26pt_PT
oaire.fundingStream9471 - RIDTI
oaire.fundingStream9471 - RIDTI
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