Pre-clinical antitumour evaluation of Biphosphinic Palladacycle Complex in human leukaemia cells

dc.creatorOliveira, CR
dc.creatorBarbosa, CMV
dc.creatorNascimento, FD
dc.creatorLanetzki, CS
dc.creatorMeneghin, MB
dc.creatorPereira, FEG
dc.creatorParedes-Gamero, EJ
dc.creatorFerreira, AT
dc.creatorRodrigues, T
dc.creatorQueiroz, MLS
dc.creatorCaires, ACF
dc.creatorTersariol, ILS
dc.creatorBincoletto, C
dc.date2009
dc.dateFEB 12
dc.date2014-11-14T05:28:17Z
dc.date2015-11-26T16:04:38Z
dc.date2014-11-14T05:28:17Z
dc.date2015-11-26T16:04:38Z
dc.date.accessioned2018-03-28T22:53:45Z
dc.date.available2018-03-28T22:53:45Z
dc.identifierChemico-biological Interactions. Elsevier Ireland Ltd, v. 177, n. 3, n. 181, n. 189, 2009.
dc.identifier0009-2797
dc.identifierWOS:000263584900002
dc.identifier10.1016/j.cbi.2008.10.034
dc.identifierhttp://www.repositorio.unicamp.br/jspui/handle/REPOSIP/81203
dc.identifierhttp://www.repositorio.unicamp.br/handle/REPOSIP/81203
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/81203
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1265535
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.descriptionPrevious studies reported by Our group have introduced a new antitumoural drug called Biphosphinic Palladacycle Complex (BPC). In this paper we show that BPC causes apoptosis in leukaemia cells (HL60 and Jurkat), but not in normal human lymphocytes. IC(50) values obtained for both cell lines using the MTT and trypan blue exclusion assays 5 h after BPC treatment were lower than 8.0 mu M. Using metachromatic fluorophore, acridine orange, we observed that BPC elicited lysosomal rupture of leukaemic cells. Furthermore, BPC triggered caspase-3 and caspase-6 activation and apoptosis in cell lines, inducing chromatin condensation, apoptotic bodies, and DNA fragmentation. Interestingly, the lysosomal cathepsin B inhibitor CA074 markedly decreased BPC-induced caspase-3 and caspase-6 activation as well as cell death. Lysosomal BPC-induced membrane destabilisation was not dependent on reactive oxygen species generation, which was consistent with the absence of cellular HL60 and Jurkat membrane lipid peroxidation. We conclude that, following BPC treatment, lysosomal membrane rupture precedes cell death and the apoptotic signalling pathway is initiated by the release of cathepsin B in the cytoplasm of leukaemia cells. As no toxic effects for human lymphocytes were observed, we suggest that BPC is more selective for transformed cells, mainly due to their exacerbated lysosome expression. (C) 2008 Elsevier Ireland Ltd. All rights reserved.
dc.description177
dc.description3
dc.description181
dc.description189
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.descriptionFAEP/Universidade de Mogi das Cruzes
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.descriptionFAPESP [99/00639-2]
dc.languageen
dc.publisherElsevier Ireland Ltd
dc.publisherClare
dc.publisherIrlanda
dc.relationChemico-biological Interactions
dc.relationChem.-Biol. Interact.
dc.rightsfechado
dc.rightshttp://www.elsevier.com/about/open-access/open-access-policies/article-posting-policy
dc.sourceWeb of Science
dc.subjectBPC
dc.subjectHuman leukaemia cells
dc.subjectApoptosis
dc.subjectLysosome
dc.subjectTumor-necrosis-factor
dc.subjectAcridine-orange
dc.subjectMembrane Permeabilization
dc.subjectCathepsin-d
dc.subjectApoptosis
dc.subjectCancer
dc.subjectDeath
dc.subjectActivation
dc.subjectLysosomes
dc.subjectProtease
dc.titlePre-clinical antitumour evaluation of Biphosphinic Palladacycle Complex in human leukaemia cells
dc.typeArtículos de revistas


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