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Blood, 1 September 2004, Vol. 104, No. 5, pp. 1459-1464. Prepublished online as a Blood First Edition Paper on May 6, 2004; DOI 10.1182/blood-2004-02-0594. This Article Full Text (PDF) All Versions of this Article: 2004-02-0594v1 104/5/1459    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Ferreira, C. V Articles by Peppelenbosch, M. P Search for Related Content PubMed PubMed Citation Articles by Ferreira, C. V Articles by Peppelenbosch, M. P Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted February 19, 2004 Accepted April 17, 2004 Molecular mechanism of violacein-mediated human leukemia cell death Carmen V Ferreira, Carina L Bos, Henri H Versteeg, Giselle Z Justo, Nelson Duran, and Maikel P Peppelenbosch* Bioquimica, Universidade Estadual de Campinas, Campinas, Sao Paulo, Brazil; Experimental Internal Medicine, Academic Medical Center, Amsterdam, Netherlands Antilles Experimental Internal Medicine, Academic Medical Center, Amsterdam, Netherlands Antilles Bioquimica, Universidade Estadual de Campinas, Campinas, Sao Paulo, Brazil Biological Chemistry Laboratory, Universidade Estadual de Campinas, Campinas, Sao Paulo, Brazil; Nucleo de Ciencias Ambientais, Universidade de Mogi das Cruzes, Mogi das Cruzes, Sao Paulo, Brazil * Corresponding author; email: m.p.peppelenbosch{at}amc.uva.nl. Violacein, a pigment isolated from Chromobacterium violaceum in the Amazon river, presents diverse biological 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 NF-B target genes, and p38 MAP kinase activation. Thus, violacein effects resemble TNF signal transduction in these cells. Accordingly, infliximab, an antibody that antagonizes TNF-induced signaling abolished the biological activity of violacein. Moreover, violacein directly activated TNF receptor 1 signaling since a violacein-dependent association of Traf-2 to this TNF receptor was observed in co-immunoprecipitation experiments. Hence, violacein represents the first member of a novel class of cytotoxic drugs mediating apoptosis of HL60 cells via the specific activation of TNF receptor 1. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. C. P. Lopes, Y. C. Blanco, G. Z. Justo, P. A. Nogueira, F. L. S. Rodrigues, U. Goelnitz, G. Wunderlich, G. Facchini, M. Brocchi, N. Duran, et al. Violacein Extracted from Chromobacterium violaceum Inhibits Plasmodium Growth In Vitro and In Vivo Antimicrob. Agents Chemother., May 1, 2009; 53(5): 2149 - 2152. [Abstract] [Full Text] [PDF] K. S. Ryan, C. J. Balibar, K. E. Turo, C. T. Walsh, and C. L. Drennan The Violacein Biosynthetic Enzyme VioE Shares a Fold with Lipoprotein Transporter Proteins J. Biol. Chem., March 7, 2008; 283(10): 6467 - 6475. [Abstract] [Full Text] [PDF] L. L. Kodach, C. L. Bos, N. Duran, M. P. Peppelenbosch, C. V. Ferreira, and J. C.H. Hardwick Violacein synergistically increases 5-fluorouracil cytotoxicity, induces apoptosis and inhibits Akt-mediated signal transduction in human colorectal cancer cells Carcinogenesis, March 1, 2006; 27(3): 508 - 516. [Abstract] [Full Text] [PDF]

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