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Type: Artigo de periódico
Title: Growth Inhibitory Activity Of A Novel Lectin From Cliona Varians Against K562 Human Erythroleukemia Cells
Author: Queiroz A.F.S.
Silva R.A.
Moura R.M.
Dreyfuss J.L.
Paredes-Gamero E.J.
Souza A.C.S.
Tersariol I.L.S.
Santos E.A.
Nader H.B.
Justo G.Z.
De Sales M.P.
Abstract: Purpose: 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 μg 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 IC50 values of 70 and 100 μg 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 effect. Furthermore, we found upregulation of tumor necrosis factor receptor 1 (TNFR1) and down-modulation of p65 subunit of nuclear factor kappa B (NFκB) 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 antileukemic effect 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. © 2008 Springer-Verlag.
Citation: Cancer Chemotherapy And Pharmacology. , v. 63, n. 6, p. 1023 - 1033, 2009.
Rights: fechado
Identifier DOI: 10.1007/s00280-008-0825-4
Date Issue: 2009
Appears in Collections:Unicamp - Artigos e Outros Documentos

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