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Isololiolide, a carotenoid metabolite isolated from the brown alga Cystoseira tamariscifolia, is cytotoxic and able to induce apoptosis in hepatocarcinoma cells through caspase-3 activation, decreased Bcl-2 levels, increased p53 expression and PARP cleavage

2016-05Journal article Open access
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dc.contributor.authorVizetto-Duarte, C
dc.contributor.authorCustódio, Luísa
dc.contributor.authorGangadhar, Katkam N.
dc.contributor.authorLago, João Henrique G.
dc.contributor.authorDias, Catarina
dc.contributor.authorMatos, Ana Marta
dc.contributor.authorNeng, Nuno
dc.contributor.authorNogueira, José Manuel Florêncio
dc.contributor.authorBarreira, Luísa
dc.contributor.authorAlbericio, Fernando
dc.contributor.authorRauter, Amelia P.
dc.contributor.authorVarela, João
dc.date.accessioned2017-04-07T15:56:39Z
dc.date.available2017-04-07T15:56:39Z
dc.date.issued2016-05
dc.description.abstractBackground: Brown macroalgae have attracted attention because they display a wide range of biological activities, including antitumoral properties. In this study we isolated isololiolide from Cystoseira tamariscifolia for the first time.Purpose: To examine the therapeutical potential of isololiolide against tumor cell lines.Methods/Study design: The structure of the compound was established and confirmed by 1D and 2D NMR as well as HRMS spectral analysis. The in vitro cytotoxicity was analyzed by colorimetric 3-(4,5-dimethylthiazol- 2-yl)-2,5-diphenyltetrazolium bromide assay in tumoral as well as in non-tumoral cell lines. Cell cycle arrest and induction of apoptosis were assessed by flow cytometry. Alteration of expression levels in proteins important in the apoptotic cascade was analyzed by western blotting.Results: Isololiolidewas isolated for the first time from the brown macroalga C. tamariscifolia. Isololiolide exhibited significant cytotoxic activity against three human tumoral cell lines, namely hepatocarcinoma HepG2 cells, whereas no cytotoxicity was found in non-malignant MRC-5 and HFF-1 human fibroblasts. Isololiolide completely disrupted the HepG2 normal cell cycle and induced significant apoptosis. Moreover, western blot analysis showed that isololiolide altered the expression of proteins that are important in the apoptotic cascade, increasing PARP cleavage and p53 expression while decreasing procaspase-3 and Bcl-2 levels.Conclusion: Isololiolide isolated from C. tamariscifolia is able to exert a selective cytotoxic activity on hepatocarcinoma HepG2 cells as well as induce apoptosis through the modulation of apoptosis-related proteins. (C) 2016 Elsevier GmbH. All rights reserved.
dc.identifier.doi10.1016/j.phymed.2016.02.008
dc.identifier.issn0944-7113
dc.identifier.urihttp://hdl.handle.net/10400.1/9486
dc.language.isoeng
dc.peerreviewedyes
dc.relationMarine photosynthetic organisms of the Algarve coast with biomedical applications
dc.relationHalophytes: a precious resource of nutritional elements and bioactive compounds
dc.relationBiomedical properties of Cystoseira species: insights into nutra- and pharmaceutical applications
dc.relation.isbasedonWOS:000373824600013
dc.titleIsololiolide, a carotenoid metabolite isolated from the brown alga Cystoseira tamariscifolia, is cytotoxic and able to induce apoptosis in hepatocarcinoma cells through caspase-3 activation, decreased Bcl-2 levels, increased p53 expression and PARP cleavage
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleMarine photosynthetic organisms of the Algarve coast with biomedical applications
oaire.awardTitleHalophytes: a precious resource of nutritional elements and bioactive compounds
oaire.awardTitleBiomedical properties of Cystoseira species: insights into nutra- and pharmaceutical applications
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FMAR%2F103957%2F2008/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FMAR-EST%2F4346%2F2012/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FBD%2F81425%2F2011/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/SFRH/SFRH%2FBDE%2F51998%2F2012/PT
oaire.citation.endPage557
oaire.citation.issue5
oaire.citation.startPage550
oaire.citation.titlePhytomedicine
oaire.citation.volume23
oaire.fundingStream3599-PPCDT
oaire.fundingStream3599-PPCDT
oaire.fundingStreamSFRH
person.familyNameVizetto-Duarte
person.familyNameCustódio
person.familyNameBarreira
person.familyNameVarela
person.givenNameCatarina
person.givenNameLuísa
person.givenNameLuísa
person.givenNameJoão
person.identifier.ciencia-id791B-C560-AEA2
person.identifier.ciencia-id6D1A-17E5-1400
person.identifier.orcid0000-0002-8203-7231
person.identifier.orcid0000-0003-4338-7703
person.identifier.orcid0000-0002-4077-855X
person.identifier.orcid0000-0003-3101-693X
person.identifier.ridM-6101-2013
person.identifier.ridM-4223-2013
person.identifier.scopus-author-id15831018900
person.identifier.scopus-author-id55741416000
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
rcaap.rightsopenAccess
rcaap.typearticle
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