Xilanas de sabugo de milho como agente antioxidante, citotóxico, anticoagulante e imunomodulador

Prospecting pharmacological active polysaccharides from agricultural byproducts, such as corncobs, is an underexplored practice in the scientific community. Thus, this work aims to expand knowledge about pharmacological activities of polysaccharides extracted from corncobs. From corn cob flour a extract was obtained by ultrasound waves in an alkaline medium, and the end of the process the product was termed PECC (polysaccharidic extract from corncobs). This extract was physicochemical characterized and evaluated by in vitro assays as an antioxidant, cytotoxic, anticoagulant and imunomodulator agent. Results indicated significant activity metal chelating by PECC, and the use of PECC in cell culture cells showed no toxic effects to normal cell lines, but toxic action against HeLa tumor cells due promoting cell death by apoptosis. In addition, other pharmacological effects were observed, the PECC decreased nitric oxide (NO) production by activated macrophages, and prolonged blood clotting time through APTT assay. Then methanolic, ethanolic and ketone fractions were obtained from fractionation of PECC polysaccharides. Five methanolic fractions, six ethanolic fractions and two ketones were obtained; and all fractions were evaluated for antioxidant, cytotoxic, anticoagulant, immunomodulatory activities. E1.4 fraction exhibited significant metal chelating effect, a toxic action to induce apoptosis in HeLa cells, decreased NO production by activated macrophages, and extended blood clotting time. These results showed that the PECC pharmacological active polysaccharides would be present in the fraction E1.4. From fractionation of E1.4 polysaccharide six subfractions with different sizes were obtained: <3; 3-10; 10-30; 30-50; 50-100 and >100 KDa. About 80% of E1.4 polysaccharides had lower size to 10 KDa, and all the subfractions showed over 61% sugar in their chemical compositions. These subfractions exhibited different monosaccharide compositions, but xylose was presented in all of them. The subfractions exhibited distinct pharmacological effects in in vitro assays. Smaller subfractions (<30 KDa) had highest metal chelating activity and greater toxic action in tumor cells. The intermediate fractions (between 30-100 KDa) decreased more NO production of activated macrophages, for other side, the larger size (>100 KDa) modulated a greater number of inflammatory cytokines, and the had greatest anticoagulant effect. Therefore, when analyzing all the results together it is evident that the PECC pharmacological polysaccharides are heteroxylans, and were concentrated in E1.4 fraction, and heteroxilanas pharmacological effects depends on their molecular size. Thus, corncobs could be used as source from molecules with biotechnology potential

Indução de morte celular em células de adenocarcinoma cervical humano (HeLa) pela lectina da esponja Cinachyrella apion (CaL)

Cancer is a term used to represent a set of more than 100 diseases, including malignant tumors from different locations. The malignancies are the second leading cause of death in the population, representing approximately 17% of deaths of known cause. Strategies that induce differentiation have had limited success in the treatment of established cancers. In this work, a lectin purified from the marine sponge Cinachyrella apion (CaL) was evaluated due to its hemolytic, cytotoxic and antiproliferative properties, besides the ability to induce cell death via apoptosis in tumor cells. The antiproliferative activity of CaL was tested against cell lines, with the highest inhibition of tumor growth for HeLa, reducing cell growth at a dose dependent manner, with a concentration of 10 μg/mL. The hemolytic activity and toxicity against peripheral blood cells were tested using the concentration of IC50 for both trials and twice the IC50 for analysis in flow cytometry, indicating that CaL is not toxic to these cells. To assess the mechanism of cell death caused by CaL in HeLa cells, we performed flow cytometry and western blotting. The results showed the lectin probably induces cell death by apoptosis activation by pro-apoptotic protein Bax, promoting mitochondrial membrane permeabilization, cell cycle arrest in S phase, with accumulation of cells of approximately 57% in this phase, and acting as both dependent and/or independent of caspases pathway. These results suggest that CaL has the potential to be used as drug treatment against cancer.