Atividade antitumoral do extrato de chá verde (Camellia sinensis) em células de câncer de mama cultivadas em modelo tridimensional

Abstract

Despite advances in diagnostic and treatment, breast cancer remains the leading cause of death in more than 100 countries, including Brazil. Reducing the risk of breast cancer through a diet rich in in natura foods has been reported, with emphasis on the chemopreventive potential of green tea catechins. However, studies conducted with these bioactive compounds are mostly based on commercial formulations containing isolated catechins, and there is an interest in investigating the anticancer effects from the food matrix, which has advantages over isolated compounds. Studies in the literature have shown that some proteins of important pathways for tumor control, such as cell cycle and migration, are targets of green tea catechins, however, there is a gap in the investigation of such processes in three-dimensional (3D) culture models, that best mimic the tumor in vivo. Therefore, this study aimed to investigate the antitumor activity of green tea extract (GTE) on MCF-7 breast tumor cell spheroids. An infusion of green tea leaves (1 g: 40 mL/ 80 °C: 5 min) was obtained and lyophilized and the GTE was characterized for its main catechins. MCF-7 spheroids (5 x 103 cells/mL) were exposed to GTE (162, 324, 648, 1296 and 2592 µg/mL) and the consequences on formation, morphology, size, cell viability, migration and p21 protein expression were studied. Despite the subtle action on viability, GTE treatment reduced the size of the spheroids and completely inhibited cell migration within 24 h. An increase in p21 expression was also observed, which may indicate a relationship with cell cycle control. Furthermore, the formation of spheroids in the presence of GTE resulted in anomalous structures. The data also showed more expressive effects of GTE on the morphology and size of the spheroids when compared to exposure to EGCG (7.8, 16.6, 31.2 and 62.5 µg/mL), demonstrating the advantage of the food matrix. No cytotoxic effects were observed on MCF-10A non-tumor spheroids, confirming the selectivity of GTE for the tumor lineage. Compared to viability assays in 2D culture, the data show lower sensitivity of spheroids to GTE, thus exposing the relevance of using this cell culture model in the study of bioactive compounds for therapeutic purposes. Preliminary in vivo studies suggested that GTE treatment promoted latency of MCF-7 xenografts and further trials should be conducted to confirm these findings.