RESUMO
A new source of pectin with a cytotoxic effect on glioblastoma cells is presented. A homogeneous GWP-FP-S fraction (Mw of 29,170â¯gâ¯mol-1) was obtained by fractionating the crude pectin extract (GW) from Campomanesia xanthocarpa pulp. According to the monosaccharide composition, the GWP-FP-S was composed of galacturonic acid (58.8%), arabinose (28.5%), galactose (11.3%) and rhamnose (1.1%), comprising 57.7% of homogalacturonans (HG) and 42.0% of type I rhamnogalacturonans (RG-I). These structures were characterized by chromatographic and spectroscopic methods; GW and GWP-FP-S fractions were evaluated by MTT and crystal violet assays for their cytotoxic effects. Both fractions induced cytotoxicity (15.55-37.65%) with concomitant increase in the cellular ROS levels in human glioblastoma cells at 25-400⯵g mL-1, after 48â¯h of treatment, whereas no cytotoxicity was observed for normal NIH 3T3 cells. This is the first report of in vitro bioactivity and the first investigation of the antitumor potential of gabiroba pectins.
Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Glioblastoma/patologia , Pectinas/química , Pectinas/farmacologia , Pimenta/química , Antineoplásicos/isolamento & purificação , Linhagem Celular Tumoral , Humanos , Espaço Intracelular/efeitos dos fármacos , Espaço Intracelular/metabolismo , Monossacarídeos/análise , Pectinas/isolamento & purificação , Espécies Reativas de Oxigênio/metabolismoRESUMO
Metastasis is responsible for the majority of deaths among patients with malignant melanoma. Despite recent advances, the majority of current and modern therapies are ineffective and/or financially unfeasible. Thus, in this study, we investigated two lowcost highlydiluted natural complexes (HDNCs) that have been shown to be effective against malignant melanoma in a murine model in vivo. The aim of this study was to determine the mechanisms through which these HDNCs directly affect melanoma cells, either alone or in an artificial tumor microenvironment, suppressing the metastatic phenotype, thus explaining previous in vivo effects. For this purpose, HDNC in vitro treatments of B16F10 melanoma cells, alone or in coculture with Balb/3T3 fibroblasts, were carried out. Molecular biology techniques and standard functional assays were used to assess the changes in molecule expression and in cell behaviors related to the metastatic phenotype. Melanoma progression features were found to be regulated by HDNCs. Molecules related to cell adhesion (Ncadherin, ß1integrin and CD44), and migration, extracellular matrix remodeling and angiogenesis were modulated. The cell migratory, invasive and clonogenic capacities were reduced by the HDNCs. No loss of cell proliferation or viability were observed. On the whole, the findings of this study indicate that HDNCs directly reprogram, molecularly and functionally, melanoma cells in vitro, modulating their metastatic phenotype. Such findings are likely to be responsible for the attenuation of tumor growth and lung colonization previously observed in vivo.