Cytotoxicity of goniothalamin enantiomers in renal cancer cells: Involvement of nitric oxide, apoptosis and autophagy

dc.creatorde Fatima, A
dc.creatorZambuzzi, WF
dc.creatorModolo, LV
dc.creatorTarsitano, CAB
dc.creatorGadelha, FR
dc.creatorHyslop, S
dc.creatorde Carvalho, JE
dc.creatorSalgado, I
dc.creatorFerreira, CV
dc.creatorPilli, RA
dc.date2008
dc.date45962
dc.date2014-11-18T17:32:50Z
dc.date2015-11-26T17:52:53Z
dc.date2014-11-18T17:32:50Z
dc.date2015-11-26T17:52:53Z
dc.date.accessioned2018-03-29T00:36:24Z
dc.date.available2018-03-29T00:36:24Z
dc.identifierChemico-biological Interactions. Elsevier Ireland Ltd, v. 176, n. 41700, n. 143, n. 150, 2008.
dc.identifier0009-2797
dc.identifierWOS:000261557600009
dc.identifier10.1016/j.cbi.2008.08.003
dc.identifierhttp://www.repositorio.unicamp.br/jspui/handle/REPOSIP/57641
dc.identifierhttp://www.repositorio.unicamp.br/handle/REPOSIP/57641
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/57641
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1290372
dc.descriptionGoniothalamin is a styryllactone synthesized by plants of the genus Goniothalamus. The biological activities of this molecule, particularly its anti-protozoan, anti-fungal, and larvicidal properties, have received considerable attention. In this work, we investigated the action of the natural and synthetic enantiomers (R)-goniothalamin (1) and (S)-goniothalamin (ent-1) on cell viability. nitric oxide synthase (NOS) expression and activity, and the expression of selected proteins involved in apoptosis and autophagy in renal cancer cells. Both compounds were cytotoxic and decreased the mitochondrial function of renal cancer cells. However, the enantiomers differentially affected the expression/activity profiles of some signaling pathway mediators. Ent-1 (4 nM) was more potent than 1 (6.4 mu M) in inhibiting constitutive NOS activity (54% and 59% inhibition, respectively), and both enantiomers decreased the protein expression of neuronal and endothelial NOS, as assessed by western blotting. Ent-1 and 1 caused down-regulation of Ras and TNFR1 and inhibition of protein serine/threonine phosphatase 2A (MA). Compound 1 markedly down-regulated Bcl2, an anti-apoptotic protein, and also induced PARP cleavage. Despite inducing an expressive down-regulation of Bax, ent-1 was also able to induce PARP cleavage. These results suggest that these compounds caused apoptosis in renal cancer cells. Interestingly. ent-1 enhanced the expression of LC3, a typical marker of autophagy. NF kappa B was clown-regulated in 1-treated cells. Overall, these results indicate that the anti-proliferative activity of the two enantiomers on renal cancer cells involved distinct signaling pathways. apoptosis and autophagy as dominant responses towards 1 and ent-1, respectively. (C) 2008 Elsevier Ireland Ltd. All rights reserved.
dc.description176
dc.description41700
dc.description143
dc.description150
dc.languageen
dc.publisherElsevier Ireland Ltd
dc.publisherClare
dc.publisherIrlanda
dc.relationChemico-biological Interactions
dc.relationChem.-Biol. Interact.
dc.rightsfechado
dc.rightshttp://www.elsevier.com/about/open-access/open-access-policies/article-posting-policy
dc.sourceWeb of Science
dc.subjectApoptosis
dc.subjectAutophagy
dc.subjectGoniothalamin enantiomers
dc.subjectNitric oxide
dc.subjectRenal cancer
dc.subjectStyryl-lactone Derivatives
dc.subjectNecrosis-factor-alpha
dc.subjectHuman Breast-cancer
dc.subjectSynthase Activity
dc.subjectLeukemia-cells
dc.subjectExpression
dc.subjectMechanisms
dc.subjectDisease
dc.subjectTumors
dc.subjectLines
dc.titleCytotoxicity of goniothalamin enantiomers in renal cancer cells: Involvement of nitric oxide, apoptosis and autophagy
dc.typeArtículos de revistas


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