RESUMEN
Brazilian propolis has been widely studied in recent years. Considering the lack of data concerning the effects of Brazilian propolis on human umbilical vein endothelial cells (HUVECs), we examined the effects of ethanol-extracted Brazilian propolis (EEBP) at 12.5, 25 and 50 µg/ml on apoptosis of HUVECs deprived of basic fibroblast growth factor (FGF-2) and serum. A high concentration of the extract induced HUVEC apoptosis at 24h. Furthermore, we investigated the molecular mechanisms of HUVEC apoptosis induced by EEBP by testing the levels of integrin ß4, p53, reactive oxygen species (ROS) and mitochondrial membrane potential. A low concentration of EEBP (12.5 µg/ml) could decrease the expression of integrin ß4, p53 and ROS levels, whereas high concentrations (25 and 50 µg/ml) could increase the levels of integrin ß4, p53 and ROS at 24h and depress mitochondrial membrane potential level at all times. Considering the doses and the results obtained in this study, Brazilian propolis at high concentrations may be an apoptosis-inducing agent associated with the signal pathway mediated by integrin ß4, p53, ROS and mitochondrial membrane potential, thus, propolis should be used in safer levels for human health.
Asunto(s)
Apoptosis/efectos de los fármacos , Endotelio Vascular/efectos de los fármacos , Própolis/farmacología , Venas Umbilicales/efectos de los fármacos , Western Blotting , Células Cultivadas , Relación Dosis-Respuesta a Droga , Endotelio Vascular/citología , Endotelio Vascular/metabolismo , Técnica del Anticuerpo Fluorescente , Humanos , Integrina beta4/metabolismo , Potenciales de la Membrana , Especies Reactivas de Oxígeno/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Venas Umbilicales/citología , Venas Umbilicales/metabolismoRESUMEN
Pleomorphic adenoma (PA) and adenoid cystic carcinoma (ACC) are the commonest benign and malignant salivary gland tumours respectively. Interactions between cells and extracellular matrix of PA and ACC, partially mediated by integrins, are important in their biology. The expression of integrins is regulated by numerous factors, amongst them, transforming growth factor beta1 (TGFbeta1). Our study investigated the effects of TGFbeta1 on the expression of integrin beta subunits in vitro and on the expression of cytoskeletal proteins of cells derived from PA and ACC. The expression of cytoskeletal differentiation markers and integrins was assessed using immunofluorescence. ELISA assays were employed to quantitate the expression integrins and MTT assays evaluated the mitochondrial activity of cells stimulated with TGFbeta1. PA cells showed increased expression of integrins and de novo expression of differentiation markers upon TGFbeta1 stimulation. ACC cells were less responsive to such stimulation. This may reflect important differences in the biological behaviour of benign and malignant cells.