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dc.contributor.authorFerreira, José Roberto Oliveira-
dc.contributor.authorCavalcanti, Bruno Coêlho-
dc.contributor.authorCosta, Patricia Marçal da-
dc.contributor.authorArantes, Francisco Frederico Perlinson de-
dc.contributor.authorAlvarenga, Elson Santiago de-
dc.contributor.authorMaltha, Célia Regina Alvares-
dc.contributor.authorBarbosa, Luiz Cláudio de Almeida-
dc.contributor.authorMilitão, Gardenia Carmen Gadelha-
dc.contributor.authorPessoa, Claúdia-
dc.contributor.authorFerreira, Paulo Michel Pinheiro-
dc.identifier.citationFERREIRA, J. R. O. et al. Induction of G2/M arrest, caspase activation and apoptosis by a-santonin derivatives in HL-60 cells. Toxicology in vitro, Oxford, Inglaterra, GB, v. 27, n. 5, p. 1458-1466, ago. 2013.pt_BR
dc.description.abstractSesquiterpene lactones (SLs) are natural products with a variety of biological activities. Previously, we demonstrated the cytotoxic effects of three new a-santonin derivatives on different tumor cell lines with low toxic effects upon peripheral human leukocytes. Here, we evaluated the mechanism of action triggered by these derivatives. HL-60 cell cycle determined after 24 h treatment revealed a significant inhibition on cell-cycle progression and leading to an increasing of cells in G2/M [7.6% and 9.0% for compound 3% and 9.0% and 8.6% for compound 4 (1 and 2 lM, respectively)]. However, after 48 h exposure, all compounds caused G2/M reduction and a significant DNA fragmentation. Compounds 2, 3 and 4 were able to induce apoptosis on leukemia cells, which was corroborated by phosphatidyserine externalization and activation of caspases-3 and -7 after 24 h exposure. None of the derivatives analyzed caused depolarization of mitochondrial membrane within 24 h of incubation, suggesting the involvement of the extrinsic apoptotic pathway in the death process. The antiproliferative action of these compounds is related to the DNA synthesis inhibition and cell cycle arrest, which probably lead to apoptosis activation. Therefore, these santonin derivatives are promising lead candidates for development of new cytotoxic agents.pt_BR
dc.publisherToxicology in vitropt_BR
dc.subjectCitotoxicidade Imunológicapt_BR
dc.titleInduction of G2/M arrest, caspase activation and apoptosis by a-santonin derivatives in HL-60 cellspt_BR
dc.typeArtigo de Periódicopt_BR
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