Growth inhibitory activity of a novel lectin from Cliona varians against K562 human erythroleukemia cells

dc.creatorQueiroz, AFS
dc.creatorSilva, RA
dc.creatorMoura, RM
dc.creatorDreyfuss, JL
dc.creatorParedes-Gamero, EJ
dc.creatorSouza, ACS
dc.creatorTersariol, ILS
dc.creatorSantos, EA
dc.creatorNader, HB
dc.creatorJusto, GZ
dc.creatorde Sales, MP
dc.date2009
dc.dateMAY
dc.date2014-11-13T13:26:13Z
dc.date2015-11-26T17:09:44Z
dc.date2014-11-13T13:26:13Z
dc.date2015-11-26T17:09:44Z
dc.date.accessioned2018-03-28T23:58:21Z
dc.date.available2018-03-28T23:58:21Z
dc.identifierCancer Chemotherapy And Pharmacology. Springer, v. 63, n. 6, n. 1023, n. 1033, 2009.
dc.identifier0344-5704
dc.identifierWOS:000265257300006
dc.identifier10.1007/s00280-008-0825-4
dc.identifierhttp://www.repositorio.unicamp.br/jspui/handle/REPOSIP/68505
dc.identifierhttp://www.repositorio.unicamp.br/handle/REPOSIP/68505
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/68505
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1280693
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.descriptionCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.descriptionPurpose In this study, the antitumoral potential of a novel lectin (CvL) purified from the marine sponge Cliona varians was studied in different cancer cell lines. Methods CvL cytotoxicity was evaluated in mammalian tumor cells and in normal human peripheral blood lymphocytes by the MTT assay using the same range of concentrations (1 - 150 mu g ml(-1)). The mechanisms involved in K562 cell death were investigated by confocal fluorescence microscopy, flow cytometry and immunoblot. Results CvL inhibited the growth of human leukemia cells, with IC(50) values of 70 and 100 mu g ml(-1) for K562 and JURKAT cells, respectively, but it was ineffective on blood lymphocytes and solid tumor cell lines. K562 cell death occurred 72 h after exposure to the lectin and with signs of apoptosis, as analyzed by DAPI and annexin V/PI staining. Investigation of the possible mediators of this process showed that cell death occurred via a caspase-independent pathway. Confocal fluorescence microscopy indicated a pivotal role for the lysosomal protease cathepsin B in mediating cell death. Accordingly, pre-incubation of K562 cells with the cathepsin inhibitor L-trans-epoxysuccinyl-L-leucylamido-(4-guanidino) butane (E-64) abolished CvL cytotoxic eVect. Furthermore, we found upregulation of tumor necrosis factor receptor 1 (TNFR1) and down-modulation of p65 subunit of nuclear factor kappa B ( NF kappa B) expression in CvL-treated cells. These effects were accompanied by increased levels of p21 and reduced expression of pRb, suggesting that CvL can induce cell cycle arrest. Conclusions Collectively, these findings indicate an anti-leukemic eVect for CvL and suggest that cathepsin B acts as a death mediator in CvL-induced cytotoxicity possibly in an uncharacterized connection with the membrane death receptor pathway.
dc.description63
dc.description6
dc.description1023
dc.description1033
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.descriptionFinanciadora de Estudos e Projetos (FINEP)
dc.descriptionCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.descriptionCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.descriptionFAPESP [06/07315-3]
dc.languageen
dc.publisherSpringer
dc.publisherNew York
dc.publisherEUA
dc.relationCancer Chemotherapy And Pharmacology
dc.relationCancer Chemother. Pharmacol.
dc.rightsfechado
dc.rightshttp://www.springer.com/open+access/authors+rights?SGWID=0-176704-12-683201-0
dc.sourceWeb of Science
dc.subjectLectin
dc.subjectCliona varians
dc.subjectK562
dc.subjectApoptosis
dc.subjectCathepsin B
dc.subjectCytotoxicity
dc.subjectAntitumor
dc.subjectNf-kappa-b
dc.subjectColon-cancer Cells
dc.subjectInduced Apoptosis
dc.subjectCathepsin-b
dc.subjectDifferent Mechanisms
dc.subjectConcanavalin-a
dc.subjectIn-vitro
dc.subjectDeath
dc.subjectActivation
dc.subjectAgglutinin
dc.titleGrowth inhibitory activity of a novel lectin from Cliona varians against K562 human erythroleukemia cells
dc.typeArtículos de revistas


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