Jacaranone Induces Apoptosis in Melanoma Cells via ROS-Mediated Downregulation of Akt and p38 MAPK Activation and Displays Antitumor Activity in Vivo

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dc.contributor.authorMassaoka, Mariana Hiromi [UNIFESP]
dc.contributor.authorMatsuo, Alisson Leonardo [UNIFESP]
dc.contributor.authorFigueiredo, Carlos Rogerio [UNIFESP]
dc.contributor.authorFarias, Camyla F. [UNIFESP]
dc.contributor.authorGirola, Natalia [UNIFESP]
dc.contributor.authorArruda, Denise Costa [UNIFESP]
dc.contributor.authorScutti, Jorge Augusto Borin [UNIFESP]
dc.contributor.authorRomoff, Paulete
dc.contributor.authorFavero, Oriana A.
dc.contributor.authorFerreira, Marcelo J. P.
dc.contributor.authorLago, Joao Henrique Ghilardi [UNIFESP]
dc.contributor.authorTravassos, Luiz Rodolpho [UNIFESP]
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.contributor.institutionUniv Presbiteriana Mackenzie
dc.date.accessioned2016-01-24T14:27:21Z
dc.date.available2016-01-24T14:27:21Z
dc.date.issued2012-06-06
dc.description.abstractBackground: Malignant melanoma is a deadly type of metastatic skin cancer with increased incidence over the past 30 years. Despite the advanced knowledge on the biology, immunobiology and molecular genetics of melanoma, the alternatives of treatment are limited with poor prognosis. On clinical trials, natural products and among them redox-active quinones have been tested in the attempt to control the growth of cancer cells. Recently, we isolated jacaranone from Pentacalia desiderabilis, a benzoquinone derivative that showed a broad antitumor activity and protective anti-melanoma effect in a syngeneic model. the purified substance is active at micromolar concentrations, is not hemolytic, and is not toxic in naive mice.Methodology/Principal Findings: the jacaranone antitumor activity was shown against several human cancer cell lines in vitro. Moreover, the induction of apoptosis in murine melanoma cells and jacaranone antitumor activity in vivo, in a melanoma experimental model, were also shown. Jacaranone renders antiproliferative and proapoptotic responses in tumor cells, by acting on Akt and p38 MAPK signaling pathways through generation of reactive oxygen species (ROS). the free radical scavenger N-acetyl-cysteine (NAC) was able to completely suppress cell death induced by jacaranone as it blocked Akt downregulation, p38 MAPK activation as well as upregulation of proapoptotic Bax. Notably, treatment of melanoma growing subcutaneously in mice with jacaranone significantly extended the mean survival times in a dose-dependent manner.Conclusions/Significance: the results provide evidence for the mechanisms of action of jacaranone and emphasize the potential use of this quinone for the treatment of melanoma.en
dc.description.affiliationUniversidade Federal de São Paulo, Unidade Oncol Expt, São Paulo, Brazil
dc.description.affiliationUniv Presbiteriana Mackenzie, Ctr Ciencias & Humanidades, São Paulo, Brazil
dc.description.affiliationUniv Presbiteriana Mackenzie, Ctr Ciencias Biol & Saude, São Paulo, Brazil
dc.description.affiliationUniversidade Federal de São Paulo, Inst Ciencias Ambientais Quim & Farmaceut, Diadema, SP, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Unidade Oncol Expt, São Paulo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Inst Ciencias Ambientais Quim & Farmaceut, 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: 2010/51423-0
dc.format.extent11
dc.identifierhttp://dx.doi.org/10.1371/journal.pone.0038698
dc.identifier.citationPlos One. San Francisco: Public Library Science, v. 7, n. 6, 11 p., 2012.
dc.identifier.doi10.1371/journal.pone.0038698
dc.identifier.fileWOS000305348400087.pdf
dc.identifier.issn1932-6203
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/34988
dc.identifier.wosWOS:000305348400087
dc.language.isoeng
dc.publisherPublic Library Science
dc.relation.ispartofPlos One
dc.rightsinfo:eu-repo/semantics/openAccess
dc.titleJacaranone Induces Apoptosis in Melanoma Cells via ROS-Mediated Downregulation of Akt and p38 MAPK Activation and Displays Antitumor Activity in Vivoen
dc.typeinfo:eu-repo/semantics/article
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