Growth inhibition and pro-apoptotic activity of violacein in Ehrlich ascites tumor

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dc.contributor.authorBromberg, Natalia
dc.contributor.authorDreyfuss, Juliana L. [UNIFESP]
dc.contributor.authorRegatieri, Caio V. [UNIFESP]
dc.contributor.authorPalladino, Marcelly V. [UNIFESP]
dc.contributor.authorDuran, Nelson
dc.contributor.authorNader, Helena B. [UNIFESP]
dc.contributor.authorHaun, Marcela
dc.contributor.authorJusto, Giselle Z. [UNIFESP]
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.contributor.institutionUniversidade Estadual de Campinas (UNICAMP)
dc.date.accessioned2016-01-24T13:59:47Z
dc.date.available2016-01-24T13:59:47Z
dc.date.issued2010-06-07
dc.description.abstractThe continuing threat to biodiversity lends urgency to the need of identification of sustainable source of natural products. This is not so much trouble if there is a microbial source of the compound. Herein, violacein, a natural indolic pigment extracted from Chromobacterium violaceum, was evaluated for its antitumoral potential against the Ehrlich ascites tumor (EAT) in vivo and in vitro. Evaluation of violacein cytotoxicity using different endpoints indicated that EAT cells were twofold (IC(50) = 5.0 mM) more sensitive to the compound than normal human peripheral blood lymphocytes. in vitro studies indicated that violacein cytotoxicity to EAT cells is mediated by a rapid (8-12 h) production of reactive oxygen species (ROS) and a decrease in intracellular GSH levels, probably due to oxidative stress. Additionally, apoptosis was primarily induced, as demonstrated by an increase in Annexin-V positive cells, concurrently with increased levels of DNA fragmentation and increased caspase-2. caspase-9 and caspase-3 activities up to 4.5-, 6.0- and 5.5-fold, respectively, after 72 h of treatment. Moreover, doses of 0.1 and 1.0 mu g kg(-1) violacein, administered intraperitoneally (i.p.) to EAT-bearing mice throughout the lifespan of the animals significantly inhibited tumor growth and increased survival of mice. in view of these results, a 35-day toxicity study was conducted in vivo. Complete hematology, biochemistry (ALT, AST and creatinine levels) and histopathological analysis of liver and kidney indicated that daily doses of violacein up to 1000 mg kg(-1) for 35 days are well tolerated and did not cause hematotoxicity not renal or hepatotoxicity when administered i.p. to mice. Altogether, these results indicate that violacein causes oxidative stress and an imbalance in the antioxidant defense machinery of cells culminating in apoptotic cell death. Furthermore, this is the first report of its antitumor activity in vivo, which occurs in the absence of toxicity to major organs. (C) 2010 Elsevier Ireland Ltd. All rights reserved.en
dc.description.affiliationUniversidade Federal de São Paulo UNIFESP, Dept Bioquim, BR-04044020 São Paulo, Brazil
dc.description.affiliationUniv Estadual Campinas, UNICAMP, Biol Chem Lab, Inst Quim, BR-13083970 Campinas, SP, Brazil
dc.description.affiliationUniversidade Federal de São Paulo UNIFESP, Dept Ciencias Biol, BR-09972270 Diadema, SP, Brazil
dc.description.affiliationUniv Estadual Campinas, UNICAMP, Inst Biol, Dept Bioquim, BR-13083970 Campinas, SP, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo UNIFESP, Dept Bioquim, BR-04044020 São Paulo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo UNIFESP, Dept Ciencias Biol, BR-09972270 Diadema, SP, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorshipIDFAPESP: 00/08422-1
dc.format.extent43-52
dc.identifierhttp://dx.doi.org/10.1016/j.cbi.2010.04.016
dc.identifier.citationChemico-biological Interactions. Clare: Elsevier B.V., v. 186, n. 1, p. 43-52, 2010.
dc.identifier.doi10.1016/j.cbi.2010.04.016
dc.identifier.issn0009-2797
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/32625
dc.identifier.wosWOS:000278801500007
dc.language.isoeng
dc.publisherElsevier B.V.
dc.relation.ispartofChemico-biological Interactions
dc.rightsinfo:eu-repo/semantics/restrictedAccess
dc.rights.licensehttp://www.elsevier.com/about/open-access/open-access-policies/article-posting-policy
dc.subjectEhrlich ascites tumoren
dc.subjectViolaceinen
dc.subjectAntitumoralen
dc.subjectApoptosisen
dc.subjectChromobacterium violaceumen
dc.subjectToxicologyen
dc.titleGrowth inhibition and pro-apoptotic activity of violacein in Ehrlich ascites tumoren
dc.typeinfo:eu-repo/semantics/article
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