Navegando por Autor "Nader, Helena B."
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Artigo Anti-IIa activity and antitumor properties of a hybrid heparin/heparan sulfate-like compound from Litopenaeus vannamei shrimp(Elsevier, 2018-06-30) Brito, Adriana da Silva; Cavalcante, Rômulo S.; Cavalheiro, Renan P.; Palhares, Laís C. G. F.; Nobre, Leonardo Thiago Duarte Barreto; Souza, Giulianna Paiva Viana de Andrade; Nader, Helena B.; Lima, Marcelo A.; Chavante, Suely FerreiraIn this present study, the anti-IIa activity and the antitumor properties of a hybrid heparin/heparan sulfate-like compound (sH/HS) from Litopenaeus vannamei shrimp heads are related. In addition to inhibiting 90.7% of thrombin activity at the lowest tested concentration (0.5 μg/mL), sH/HS compound stimulated the synthesis of antithrombotic heparan sulfate by endothelial cells in a dose-dependent manner. In vitro experiments demonstrated that the molecule from shrimp displayed a potent anti-angiogenic effect, reducing over 80% of the tubular structures formation at 50 and 100 μg/mL. In addition, sH/HS compound was able to inhibit the migration of B16F10 cells at all tested concentrations without affecting the cell viability. Although the studied compound had no effect on the proliferation of such cells during a period of 24 h, it had a significant long-term antiproliferative effect, reducing about 80% of colony formation and anchorage-independent growth at 50 and 100 μg/mL concentrations. When its effectiveness was tested in vivo, it was demonstrated that sH/HS promoted a reduction of more than 90% of tumor growth. In the context of thromboembolic disorders associated with cancer, such findings make the sH/HS compound an excellent target for studies on inhibiting of development and tumor progression, and the prevention of coagulopathiesArtigo Growth inhibitory activity of a novel lectin from Cliona varians against K562 human erythroleukemia cells(Springer, 2008-09-10) 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. dePurpose 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.