Disease relevance of Violacein

• 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 [1].
• Violacein inhibits the growth of all four colon cancer cell lines tested [2].
• Violacein leads to dephosphorylation of retinoblastoma protein and activation of caspases and a pancaspase inhibitor abrogates its biological activity [2].
• However, the vanI mutant remained capable of weakly activating both bioluminescence and violacein in the E. coli and C. violaceum biosensors, respectively, indicating the existence of additional layers of AHL-mediated regulatory complexity [3].
• Purified violacein from cell extracts of C. violaceum showed high toxicity to nanoflagellates [4].

High impact information on Violacein

• 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 [1].
• Thus, violacein effects resemble tumor necrosis factor alpha (TNF-alpha) signal transduction in these cells [1].
• 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 [1].
• 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 [1].
• Molecular mechanism of violacein-mediated human leukemia cell death [1].

Chemical compound and disease context of Violacein

• Extraction of violacein from Chromobacterium violaceum provides a new quantitative bioassay for N-acyl homoserine lactone autoinducers [5].

Biological context of Violacein

• Our data provide evidence that violacein acts through the inhibition of Akt phosphorylation with subsequent activation of the apoptotic pathway and downregulation of NF-kappaB signaling [2].
• The full sequence of the 6.7 kb eDNA violacein gene cluster and the characterization of violacein and deoxyviolacein from an eDNA clone are reported here [6].
• SWI inhibited violacein production, a phenotype that is regulated by quorum sensing in Chromobacterium violaceum [7].
• In the alkaline Comet assay, violacein, when tested at concentrations ranging from 0.19 to 1.5 microM, did not induce a significant increase in DNA damage in HEp-2 and MA104 cells [8].
• In vitro, W2 strongly interfered with violacein production by Chromobacterium violaceum, and transfer of pathogenicity in Agrobacterium tumefaciens [9].

Anatomical context of Violacein

• However, violacein was positive for DNA damage in FRhK-4 cells and for both DNA damage and micronuclei in VERO cells, in a concentration-response relationship [8].
• Violacein was highly cytotoxic to V79 fibroblasts (IC50 5-12 microM) [10].
• The action of violacein against lipid peroxidation in three models of lipid membranes, including rat liver microsomes, Egg and Soy bean phosphathidylcholine liposomes were also evaluated [11].
• In addition, the 1:2 inclusion complex improved the antilipoperoxidant activity of violacein in rat liver cells exposed to t-butyl hydroperoxide, whereas the 1:1 complex was less active than violacein [12].
• Unlike in Caco-2 cells, violacein was incapable of increasing ROS levels in HT29 cells, suggesting the existence of violacein cell-type specific mechanisms [13].

Associations of Violacein with other chemical compounds

• Thus, all the carbon and nitrogen atoms in the right part of the violacein skeleton were constructed by intact incorporation of the tryptophan molecule, with decarboxylation probably occurring at a later biosynthetic stage [14].
• The goal of the present work was to evaluate the cytotoxicity of violacein and also its potential antiviral properties.The cytotoxicity of violacein was investigated by three methods: cell morphology evaluation by inverted light microscopy and cell viability tests using the Trypan blue dye exclusion method and the MTT assay [15].
• Moreover, presence of ROS scavengers such as N-acetyl-cysteine (NAC) diminishes ROS cytotoxicity induced by violacein in Caco-2 cells, indicating that violacein mediates cellular critical mechanisms in the triggering of apoptotic tumor cell death [13].

Gene context of Violacein

• Spent V. anguillarum culture supernatants stimulated bioluminescence in a recombinant lux-based Escherichia coli AHL biosensor strain, whereas they both stimulated and inhibited AHL-mediated violacein pigment production in Chromobacterium violaceum [3].
• The effects of beta-cyclodextrin (betaCD) inclusion complexation on the ability of violacein to prevent gastric ulceration in mice were studied [12].
• The reconstitution of violacein into the membranes increased its antioxidant effect [11].
• We demonstrate that violacein mediates ROS production followed by activation of Caspase-3, release of cytochrome c, and calcium release to citosol in Caco-2 cells [13].

Analytical, diagnostic and therapeutic context of Violacein

• We have developed a quantitative bioassay that measures the amount of violacein produced by this strain in response to the presence of different concentrations of various AHL molecules [5].
• Using the TUNEL method and the Feulgen reaction coupled to image analysis, violacein (5 and 10 microM) was found to trigger apoptosis but not necrosis in V79 cells [10].
• Sequence analysis and functional characterization of the violacein biosynthetic pathway from Chromobacterium violaceum [16].
• 1. Chromobacterium violaceum (strain BB-78 isolated in Brazil) produces violacein, a substance potentially useful in phototherapy and with antibiotic and trypanocide activity [17].

References