Pouterin, a novel potential cytotoxic lectin-like protein with apoptosis-inducing activity in tumorigenic mammalian cells

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dc.contributor.authorBoleti, Ana Paula de A.
dc.contributor.authorVentura, Claudio A.
dc.contributor.authorJusto, Giselle Z. [UNIFESP]
dc.contributor.authorSilva, Rodrigo A.
dc.contributor.authorSousa, Ana Carolina T. de
dc.contributor.authorFerreira, Carmen V.
dc.contributor.authorYano, Tomomasa
dc.contributor.authorMacedo, Maria Ligia R.
dc.contributor.institutionUniv Fed Mat Grosso Sul
dc.contributor.institutionUniversidade Estadual de Campinas (UNICAMP)
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.date.accessioned2016-01-24T13:51:28Z
dc.date.available2016-01-24T13:51:28Z
dc.date.issued2008-06-15
dc.description.abstractIn this study, the cytotoxicity of pouterin in tumorigenic and non-tumorigenic mammalian cell lines was investigated. We found that HeLa, Hep-2 and HT-29 tumor cells were highly sensitive to pouterin cytotoxicity in a dose-dependent manner, whereas non-tumorigenic Vero cells and human lymphocytes were relatively resistant to the protein. Among the tumor cell lines, HeLa cells showed the highest susceptibility to pouterin cytotoxicity, exhibiting a time-dependent increase in LDH leakage and an IC50 value of 5 mu g/mL. Morphological alterations such as rounding, cell shrinkage and chromatin condensation, consistent with apoptotic cell death were observed. Apoptosis induction was demonstrated by DNA fragmentation as detected by terminal dUTP nick-end labeling (TUNEL). Furthermore, HeLa cells incubated with pouterin showed disruption of the actin cytoskeleton. Western blot analysis revealed that pouterin caused increased expression of p21, thus indicating cell cycle arrest. Subsequent studies provided evidence that apoptosis may be partially explained in the activation of the tumor necrosis factor receptor 1 (TNFR1) signaling. Interestingly, a time-dependent decrease of the expression of p65 nuclear factor kappa B (NF kappa B) subunit, concomitant with a downregulation of the inhibitor of apoptosis protein 1 (IAP1) was observed, suggesting that TNFR-mediated apoptosis is the predominant pathway induced by pouterin in HeLa cells. (c) 2008 Elsevier B.V. All rights reserved.en
dc.description.affiliationUniv Fed Mat Grosso Sul, Ctr Ciencias Biol Saude, Dept Tecralogia Alimentos & Saude Publ, Lab Purificacao Prot & Suas Funcoes Biol, BR-79070900 Campo Grande, MS, Brazil
dc.description.affiliationUniv Estadual Campinas, Dept Bioquim IB, Lab Sinalizacao, BR-13083970 Campinas, SP, Brazil
dc.description.affiliationUniv Estadual Campinas, Dept Microbiol & Imunol IB, Lab Antigenos Bacterianos, BR-13083862 Campinas, SP, Brazil
dc.description.affiliationUniversidade Federal de São Paulo, Dept Bioquim, Disciplina Biol Mol, São Paulo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Dept Bioquim, Disciplina Biol Mol, São Paulo, Brazil
dc.description.sourceWeb of Science
dc.format.extent1321-1330
dc.identifierhttp://dx.doi.org/10.1016/j.toxicon.2008.03.007
dc.identifier.citationToxicon. Oxford: Pergamon-Elsevier B.V., v. 51, n. 8, p. 1321-1330, 2008.
dc.identifier.doi10.1016/j.toxicon.2008.03.007
dc.identifier.issn0041-0101
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/30734
dc.identifier.wosWOS:000257645200001
dc.language.isoeng
dc.publisherElsevier B.V.
dc.relation.ispartofToxicon
dc.rightsinfo:eu-repo/semantics/restrictedAccess
dc.rights.licensehttp://www.elsevier.com/about/open-access/open-access-policies/article-posting-policy
dc.subjectpouterinen
dc.subjectHeLa cellsen
dc.subjectapoptosisen
dc.subjectactin cytoskeletonen
dc.subjectTNF receptoren
dc.titlePouterin, a novel potential cytotoxic lectin-like protein with apoptosis-inducing activity in tumorigenic mammalian cellsen
dc.typeinfo:eu-repo/semantics/article
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