Please use this identifier to cite or link to this item: http://hdl.handle.net/10316/27756
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dc.contributor.authorSerafim, Teresa L.-
dc.contributor.authorCarvalho, Filipa S.-
dc.contributor.authorBernardo, Telma C.-
dc.contributor.authorPereira, Gonçalo C.-
dc.contributor.authorPerkins, Edward-
dc.contributor.authorHoly, Jon-
dc.contributor.authorKrasutsky, Dmytro A.-
dc.contributor.authorKolomitsyna, Oksana N.-
dc.contributor.authorKrasutsky, Pavel A.-
dc.contributor.authorOliveira, Paulo J.-
dc.date.accessioned2014-12-03T10:11:07Z-
dc.date.available2014-12-03T10:11:07Z-
dc.date.issued2014-11-01-
dc.identifier.citationSERAFIM, Teresa L. [et. al] - New derivatives of lupane triterpenoids disturb breast cancer mitochondria and induce cell death. "Bioorganic & Medicinal Chemistry". ISSN 0968-0896. Vol. 22 Nº. 21 (2014) p. 6270–6287por
dc.identifier.issn0968-0896-
dc.identifier.urihttp://hdl.handle.net/10316/27756-
dc.description.abstractNovel cationic dimethylaminopyridine derivatives of pentacyclic triterpenes were previously described to promote mitochondrial depolarization and cell death in breast and melanoma cell lines. The objective of this work was to further investigate in detail the mechanism of mitochondrial perturbations, correlating those effects with breast cancer cell responses to those same agents. Initially, a panel of tumor and non-tumor cell lines was grown in high-glucose or glucose-free glutamine-containing media, the later forcing cells to synthesize ATP by oxidative phosphorylation only. Cell proliferation, cell cycle, cell death and mitochondrial membrane polarization were evaluated. Inhibition of cell proliferation was observed, accompanied by an arrest in the G1-cell cycle phase, and importantly, by loss of mitochondrial membrane potential. On a later time-point, caspase-9 and 3 activation were observed, resulting in cell death. For the majority of test compounds, we determined that cell toxicity was augmented in the galactose media. To investigate direct evidences on mitochondria isolated rat liver mitochondria were used. The results showed that the compounds were strong inducers of the permeability transition pore. Confirming our previous results, this work shows that the novel DMAP derivatives strongly interact with mitochondria, resulting in pro-apoptotic signaling and cell death.por
dc.language.isoengpor
dc.publisherElsevierpor
dc.rightsopenAccesspor
dc.subjectBioenergeticspor
dc.subjectBreast cancerpor
dc.subjectCell deathpor
dc.subjectCytotoxicitypor
dc.subjectLupane triterpenoids derivativespor
dc.subjectMitochondrial physiologypor
dc.titleNew derivatives of lupane triterpenoids disturb breast cancer mitochondria and induce cell deathpor
dc.typearticlepor
degois.publication.firstPage6270por
degois.publication.lastPage6287por
degois.publication.issue21por
degois.publication.titleBioorganic & Medicinal Chemistrypor
dc.relation.publisherversionhttp://www.sciencedirect.com/science/article/pii/S0968089614005902por
dc.peerreviewedYespor
dc.identifier.doi10.1016/j.bmc.2014.08.013-
degois.publication.volume22por
item.fulltextCom Texto completo-
item.grantfulltextopen-
item.languageiso639-1en-
Appears in Collections:I&D CNC - Artigos em Revistas Internacionais
FCTUC Ciências da Vida - Artigos em Revistas Internacionais
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