Molecular Mechanism Of Violacein-mediated Human Leukemia Cell Death.

dc.creatorFerreira, Carmen Veríssima
dc.creatorBos, Carina L
dc.creatorVersteeg, Henri H
dc.creatorJusto, Giselle Z
dc.creatorDurán, Nelson
dc.creatorPeppelenbosch, Maikel P
dc.date2004-Sep
dc.date2015-11-27T12:58:08Z
dc.date2015-11-27T12:58:08Z
dc.date.accessioned2018-03-29T00:59:00Z
dc.date.available2018-03-29T00:59:00Z
dc.identifierBlood. v. 104, n. 5, p. 1459-64, 2004-Sep.
dc.identifier0006-4971
dc.identifier10.1182/blood-2004-02-0594
dc.identifierhttp://www.ncbi.nlm.nih.gov/pubmed/15130948
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/195792
dc.identifier15130948
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1296025
dc.descriptionViolacein, a pigment isolated from Chromobacterium violaceum in the Amazon River, presents diverse biologic properties and attracts interest as a consequence of its antileukemic activity. Elucidation of the molecular mechanism mediating this activity will provide further relevant information for understanding its effects on the cellular physiology of untransformed cells and for considering its possible clinical application. Here, we show that violacein causes apoptosis in HL60 leukemic cells but is ineffective in this respect in other types of leukemia cells or in normal human lymphocytes and monocytes. Violacein cytotoxicity in HL60 cells was preceded by activation of caspase 8, transcription of nuclear factor kappaB (NF-kappaB) target genes, and p38 mitogen-activated protein (MAP) kinase activation. Thus, violacein effects resemble tumor necrosis factor alpha (TNF-alpha) signal transduction in these cells. Accordingly, infliximab, an antibody that antagonizes TNF-alpha-induced signaling abolished the biologic activity of violacein. Moreover, violacein directly activated TNF receptor 1 signaling, because a violacein-dependent association of TNF receptor-associated factor 2 (TRAF2) to this TNF receptor was observed in coimmunoprecipitation experiments. Hence, violacein represents the first member of a novel class of cytotoxic drugs mediating apoptosis of HL60 cells by way of the specific activation of TNF receptor 1.
dc.description104
dc.description1459-64
dc.languageeng
dc.relationBlood
dc.relationBlood
dc.rightsfechado
dc.rights
dc.sourcePubMed
dc.subjectAntigens, Cd
dc.subjectCaspase 3
dc.subjectCaspases
dc.subjectCell Death
dc.subjectCell Survival
dc.subjectCyclin-dependent Kinase Inhibitor P21
dc.subjectCyclins
dc.subjectDna-binding Proteins
dc.subjectHl-60 Cells
dc.subjectHumans
dc.subjectIndoles
dc.subjectK562 Cells
dc.subjectLeukemia, Promyelocytic, Acute
dc.subjectMitogen-activated Protein Kinase 1
dc.subjectMitogen-activated Protein Kinase 3
dc.subjectMitogen-activated Protein Kinases
dc.subjectNf-kappa B
dc.subjectPhosphorylation
dc.subjectReceptors, Tumor Necrosis Factor
dc.subjectReceptors, Tumor Necrosis Factor, Type I
dc.subjectStat1 Transcription Factor
dc.subjectStat2 Transcription Factor
dc.subjectSignal Transduction
dc.subjectTrans-activators
dc.subjectU937 Cells
dc.subjectUp-regulation
dc.titleMolecular Mechanism Of Violacein-mediated Human Leukemia Cell Death.
dc.typeArtículos de revistas


Este ítem pertenece a la siguiente institución