Growth inhibitory activity of a novel lectin from Cliona varians against K562 human erythroleukemia cells
Purpose In this study, the antitumoral potential of a novel lectin (CvL) puriWed from the marine sponge Cliona varians was studied in diVerent cancer cell lines. Methods CvL cytotoxicity was evaluated in mammalian tumor cells and in normal human peripheral blood lymphocytes by the MTT assay using t...
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ri-123456789-252502021-11-11T20:56:01Z Growth inhibitory activity of a novel lectin from Cliona varians against K562 human erythroleukemia cells Queiroz, Alexandre Flavio Silva de Silva, Rodrigo A. Moura, Raniere M. Dreyfuss, Juliana L. Paredes-Gamero, Edgar J. Souza, Ana C. S. Tersariol, Ivarne L. S. Santos, Elizeu A. Nader, Helena B. Justo, Giselle Z. Sales, Maurício P. de Lectin Cliona varians K562 Apoptosis Cathepsin B Cytotoxicity Antitumor Purpose In this study, the antitumoral potential of a novel lectin (CvL) puriWed from the marine sponge Cliona varians was studied in diVerent 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 _g ml¡1). The mechanisms involved in K562 cell death were investigated by confocal Xuorescence microscopy, Xow cytometry and immunoblot. Results CvL inhibited the growth of human leukemia cells, with IC50 values of 70 and 100 _gml¡1 for K562 and JURKAT cells, respectively, but it was ineVective 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 Xuorescence 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_B) expression in CvL-treated cells. These eVects were accompanied by increased levels of p21 and reduced expression of pRb, suggesting that CvL can induce cell cycle arrest. Conclusions Collectively, these Wndings indicate an antileukemic 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. 2018-05-26T15:57:42Z 2018-05-26T15:57:42Z 2008-09-10 article Queiroz,Alexandre F. S.; Silva, Rodrigo A.;Moura, Raniere M.;Dreyfuss, Juliana L.;Paredes-Gamero, Edgar J.; Souza, Ana C. S.; Tersariol, Ivarne L. S.; Santos, Elizeu A.; Nader.Helena B.; Justo, Giselle Z.; Sales, Maurício P. de.Growth inhibitory activity of a novel lectin from Cliona varians against K562 human erythroleukemia cells.Cancer Chemotherapy and Pharmacology, v. 63, p. 1023-1033, 2009.Disponível em: <https://link.springer.com/article/10.1007/s00280-008-0825-4>. Acesso em: 05 mar. 2018. 1432-0843 https://repositorio.ufrn.br/jspui/handle/123456789/25250 10.1007/s00280-008-0825-4 eng Acesso Aberto application/pdf Springer |
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Lectin Cliona varians K562 Apoptosis Cathepsin B Cytotoxicity Antitumor |
| spellingShingle |
Lectin Cliona varians K562 Apoptosis Cathepsin B Cytotoxicity Antitumor Queiroz, Alexandre Flavio Silva de Silva, Rodrigo A. Moura, Raniere M. Dreyfuss, Juliana L. Paredes-Gamero, Edgar J. Souza, Ana C. S. Tersariol, Ivarne L. S. Santos, Elizeu A. Nader, Helena B. Justo, Giselle Z. Sales, Maurício P. de Growth inhibitory activity of a novel lectin from Cliona varians against K562 human erythroleukemia cells |
| description |
Purpose In this study, the antitumoral potential of a novel lectin (CvL) puriWed from the marine sponge Cliona varians was studied in diVerent 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 _g ml¡1). The mechanisms involved in K562 cell death were investigated by confocal Xuorescence microscopy, Xow cytometry and immunoblot.
Results CvL inhibited the growth of human leukemia cells, with IC50 values of 70 and 100 _gml¡1 for K562 and JURKAT cells, respectively, but it was ineVective 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 Xuorescence 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_B) expression in CvL-treated cells. These eVects were accompanied by increased levels of p21 and reduced expression of pRb, suggesting that CvL can induce cell cycle arrest.
Conclusions Collectively, these Wndings indicate an antileukemic 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. |
| format |
article |
| author |
Queiroz, Alexandre Flavio Silva de Silva, Rodrigo A. Moura, Raniere M. Dreyfuss, Juliana L. Paredes-Gamero, Edgar J. Souza, Ana C. S. Tersariol, Ivarne L. S. Santos, Elizeu A. Nader, Helena B. Justo, Giselle Z. Sales, Maurício P. de |
| author_facet |
Queiroz, Alexandre Flavio Silva de Silva, Rodrigo A. Moura, Raniere M. Dreyfuss, Juliana L. Paredes-Gamero, Edgar J. Souza, Ana C. S. Tersariol, Ivarne L. S. Santos, Elizeu A. Nader, Helena B. Justo, Giselle Z. Sales, Maurício P. de |
| author_sort |
Queiroz, Alexandre Flavio Silva de |
| title |
Growth inhibitory activity of a novel lectin from Cliona varians against K562 human erythroleukemia cells |
| title_short |
Growth inhibitory activity of a novel lectin from Cliona varians against K562 human erythroleukemia cells |
| title_full |
Growth inhibitory activity of a novel lectin from Cliona varians against K562 human erythroleukemia cells |
| title_fullStr |
Growth inhibitory activity of a novel lectin from Cliona varians against K562 human erythroleukemia cells |
| title_full_unstemmed |
Growth inhibitory activity of a novel lectin from Cliona varians against K562 human erythroleukemia cells |
| title_sort |
growth inhibitory activity of a novel lectin from cliona varians against k562 human erythroleukemia cells |
| publisher |
Springer |
| publishDate |
2018 |
| url |
https://repositorio.ufrn.br/jspui/handle/123456789/25250 |
| work_keys_str_mv |
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