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

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

Author Queiroz, Alexandre F. S. Google Scholar
Silva, Rodrigo A. Google Scholar
Moura, Raniere M. Google Scholar
Dreyfuss, Juliana L. Autor UNIFESP Google Scholar
Paredes-Gamero, Edgar J. Autor UNIFESP Google Scholar
Souza, Ana C. S. Google Scholar
Tersariol, Ivarne L. S. Autor UNIFESP Google Scholar
Santos, Elizeu A. Google Scholar
Nader, Helena B. Autor UNIFESP Google Scholar
Justo, Giselle Z. Autor UNIFESP Google Scholar
Sales, Mauricio P. de Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Univ Fed Rio Grande do Norte
Universidade Estadual de Campinas (UNICAMP)
Univ Mogi das Cruzes
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 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.
Keywords Lectin
Cliona varians
Cathepsin B
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Financiadora de Estudos e Projetos (FINEP)
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Grant number FAPESP: 06/07315-3
Date 2009-05-01
Published in Cancer Chemotherapy and Pharmacology. New York: Springer, v. 63, n. 6, p. 1023-1033, 2009.
ISSN 0344-5704 (Sherpa/Romeo, impact factor)
Publisher Springer
Extent 1023-1033
Access rights Closed access
Type Article
Web of Science ID WOS:000265257300006

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