A promising action of riboflavin as a mediator of leukaemia cell death

dc.creatorDe Souza, AC
dc.creatorKodach, L
dc.creatorGadelha, FR
dc.creatorBos, CL
dc.creatorCavagis, AD
dc.creatorAoyama, H
dc.creatorPeppelenbosch, MP
dc.creatorFerreira, CV
dc.date2006
dc.dateOCT
dc.date2014-11-15T05:00:17Z
dc.date2015-11-26T16:30:56Z
dc.date2014-11-15T05:00:17Z
dc.date2015-11-26T16:30:56Z
dc.date.accessioned2018-03-28T23:12:00Z
dc.date.available2018-03-28T23:12:00Z
dc.identifierApoptosis. Springer, v. 11, n. 10, n. 1761, n. 1771, 2006.
dc.identifier1360-8185
dc.identifierWOS:000240361200008
dc.identifier10.1007/s10495-006-9549-2
dc.identifierhttp://www.repositorio.unicamp.br/jspui/handle/REPOSIP/76673
dc.identifierhttp://www.repositorio.unicamp.br/handle/REPOSIP/76673
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/76673
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1270088
dc.descriptionBesides having a pivotal biological function as a component of coenzymes, riboflavin appears a promissing antitumoral agent, but the underlying molecular mechanism remains unclear. In this work, we demonstrate that irradiated riboflavin, when applied at mu M concentrations, induces an orderly sequence of signaling events finally leading to leukemia cell death. The molecular mechanism involved is dependent on the activation of caspase 8 caused by overexpression of Fas and FasL and also on mitochondrial amplification mechanisms, involving the stimulation of ceramide production by sphingomyelinase and ceramide synthase. The activation of this cascade led to an inhibition of mitogen activated protein kinases: JNK, MEK and ERK and survival mediators (PKB and IAP1), upregulation of the proapoptotic Bcl2 member Bax and downregulation of cell cycle progression regulators. Importantly, induction of apoptosis by irradiated riboflavin was leukaemia cell specific, as normal human lymphocytes did not respond to the compound with cell death. Our data indicate that riboflavin selectively activates Fas cascade and also constitutes a death receptor-engaged drug without harmful side effects in normal cells, bolstering the case for using this compound as a novel avenue for combating cancerous disease.
dc.description11
dc.description10
dc.description1761
dc.description1771
dc.languageen
dc.publisherSpringer
dc.publisherDordrecht
dc.publisherHolanda
dc.relationApoptosis
dc.relationApoptosis
dc.rightsfechado
dc.rightshttp://www.springer.com/open+access/authors+rights?SGWID=0-176704-12-683201-0
dc.sourceWeb of Science
dc.subjectriboflavin
dc.subjectphotosensitizer
dc.subjectapoptosis
dc.subjectmyeloid leukaemic cells
dc.subjectsignal transduction
dc.subjectProtein-tyrosine Phosphatases
dc.subjectAqueous-solution
dc.subjectInduced Differentiation
dc.subjectBiological Functions
dc.subjectVisible-light
dc.subjectHl60 Cells
dc.subjectApoptosis
dc.subjectCeramide
dc.subjectExpression
dc.subjectFas
dc.titleA promising action of riboflavin as a mediator of leukaemia cell death
dc.typeArtículos de revistas


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