Investigação da atividade antiglioma do ácido tânico: estudos in vitro e pré-clínico

Abstract

Cancer is a set of diseases that present a disordered cell growth invading tissues and organs, and thus enable the migration of cells to other regions of the body. Among the various types of cancer is the glioblastoma (GBM), the most common and aggressive tumor that affects the Central Nervous System (CNS), whose treatment is multimodal and surgery followed by radiotherapy and chemotherapy with temozolomide (TMZ). Considering that the GBM presents a high infiltrative capacity, high proliferation rate and chemoresistance to TMZ, it is necessary to search for new therapeutic alternatives for a better prognosis of the patients. Tannic acid (TA), is a polyphenol with antioxidant, antimicrobial and antiproliferative activity. In this work, we evaluated in vitro the antitumor and antioxidant activity of TA against GBM cells and their cytotoxicity in relation to primary astrocyte cells. Cells were exposed to different TA concentrations (6.25 to 75 μM) for 24, 48 and / or 72 h. In addition, the formation of colonies, migration and cell adhesion, type of death and cell cycle were evaluated. Subsequently, the action of TA was determined in a preclinical GBM model. In this protocol, after intracerebroventricular implantation of C6 GBM cells, Wistar rats received a dose of 50 mg/kg/day of TA through the intragastric route for 15 days. Our results demonstrated that TA showed an important antiglioma action in vitro, inducing cell death by apoptosis and cell cycle arrest, reducing formation and size of colonies, migration and cell adhesion, and demonstrating an important antioxidant effect. In the antiglioma effect in vivo, it is possible to observe that TA decreased tumor volume by 55%, accompanied by an increase in the area of intratumoral necrosis and lymphocyte infiltration, without causing systemic damage. Thus, TA can be considered a promising agent in the therapy for GBM.