Please use this identifier to cite or link to this item: http://hdl.handle.net/10316/25633
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dc.contributor.authorBernardo, Telma C.-
dc.contributor.authorCunha-Oliveira, Teresa-
dc.contributor.authorSerafim, Teresa L.-
dc.contributor.authorHoly, Jon-
dc.contributor.authorKrasutsky, Dmytro-
dc.contributor.authorKolomitsyna, Oksana-
dc.contributor.authorKrasutsky, Pavel-
dc.contributor.authorMoreno, A. J. M.-
dc.contributor.authorOliveira, Paulo J.-
dc.date.accessioned2014-04-30T10:46:05Z-
dc.date.available2014-04-30T10:46:05Z-
dc.date.issued2013-
dc.identifier.urihttp://hdl.handle.net/10316/25633-
dc.description.abstractTriterpenoids are a large class of naturally occurring compounds, and some potentially interesting as anticancer agents have been found to target mitochondria. The objective of the present work was to investigate the mechanisms of mitochondrial toxicity induced by novel dimethylaminopyridine (DMAP) derivatives of pentacyclic triterpenes, which were previously shown to inhibit the growth of melanoma cells in vitro. MCF-7, Hs 578T and BJ cell lines, as well as isolated hepatic mitochondria, were used to investigate direct mitochondrial effects. On isolated mitochondrial hepatic fractions, respiratory parameters, mitochondrial transmembrane electric potential, induction of the mitochondrial permeability transition (MPT) pore and ion transport-dependent osmotic swelling were measured. Our results indicate that the DMAP triterpenoid derivatives lead to fragmentation and depolarization of the mitochondrial network in situ, and to inhibition of uncoupled respiration, induction of the permeability transition pore and depolarization of isolated hepatic mitochondria. The results show that mitochondrial toxicity is an important component of the biological interaction of DMAP derivatives, which can explain the effects observed in cancer cells.por
dc.description.sponsorshipThis work was supported by projects Pest-C/SAU/LA0001/2013– 2014 and PTDC/QUI-QUI/101409/2008 funded by Fundação para a Ciência e a Tecnologia (FCT), Portugal, and cofinanced by: ‘COMPETE- Programa Operacional Factores de Competitividade’, QREN and European Union (FEDER-Fundo Europeu de Desenvolvimento Regional). T.C.-O. was supported by the FCT postdoctoral fellowship SFRH/BPD/34711/2007, T.L.S. supported by the FCT postdoctoral fellowship SFRH/BPD/75959/2011, both co-financed by POPHPrograma Operacional Potencial Humano, QREN and European Union.por
dc.language.isoengpor
dc.publisherElsevier Ltd.por
dc.rightsopenAccesspor
dc.subjectTriterpenoid derivativespor
dc.subjectMitochondrial permeability transitionpor
dc.subjectMitochondrial depolarizationpor
dc.subjectLiver mitochondriapor
dc.subjectBreast cancer cell linespor
dc.titleDimethylaminopyridine derivatives of lupane triterpenoids cause mitochondrial disruption and induce the permeability transitionpor
dc.typearticlepor
degois.publication.firstPage7239por
degois.publication.lastPage7249por
degois.publication.issue23por
degois.publication.titleBioorganic & Medicinal Chemistrypor
dc.relation.publisherversionhttp://www.sciencedirect.com/science/article/pii/S0968089613008559#por
dc.peerreviewedYespor
dc.identifier.doi10.1016/j.bmc.2013.09.066-
degois.publication.volume21por
uc.controloAutoridadeSim-
item.grantfulltextopen-
item.fulltextCom Texto completo-
item.languageiso639-1en-
crisitem.author.deptCNC.IBILI-
crisitem.author.deptFaculdade de Ciências e Tecnologia, Universidade de Coimbra-
crisitem.author.parentdeptUniversidade de Coimbra-
crisitem.author.researchunitCNC.IBILI-
crisitem.author.researchunitMARE - Marine and Environmental Sciences Centre-
crisitem.author.orcid0000-0002-7382-0339-
crisitem.author.orcid0000-0003-4924-5204-
crisitem.author.orcid0000-0003-3575-7604-
Appears in Collections:FCTUC Ciências da Vida - Artigos em Revistas Internacionais
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