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Type: Artigo de periódico
Title: Molecular Mechanism Of Violacein-mediated Human Leukemia Cell Death.
Author: Ferreira, Carmen Veríssima
Bos, Carina L
Versteeg, Henri H
Justo, Giselle Z
Durán, Nelson
Peppelenbosch, Maikel P
Abstract: Violacein, 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.
Subject: Antigens, Cd
Caspase 3
Cell Death
Cell Survival
Cyclin-dependent Kinase Inhibitor P21
Dna-binding Proteins
Hl-60 Cells
K562 Cells
Leukemia, Promyelocytic, Acute
Mitogen-activated Protein Kinase 1
Mitogen-activated Protein Kinase 3
Mitogen-activated Protein Kinases
Nf-kappa B
Receptors, Tumor Necrosis Factor
Receptors, Tumor Necrosis Factor, Type I
Stat1 Transcription Factor
Stat2 Transcription Factor
Signal Transduction
U937 Cells
Citation: Blood. v. 104, n. 5, p. 1459-64, 2004-Sep.
Rights: fechado
Identifier DOI: 10.1182/blood-2004-02-0594
Date Issue: 2004
Appears in Collections:Unicamp - Artigos e Outros Documentos

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