Guaraná, um fruto ultracafeinado, apresenta efeito in vitro antitumoral e na atividade quimioterápica em células de câncer colorretal e de mama

Abstract

Introduction: Colorectal (CRC) and breast cancer are considered the most incidents in the entire world. Antioxidant extracts are largely used to prevent mutations and neoplasia as well as in patients undergoing the chemotherapy treatment, such as the Paullinia cupana (guaraná). A previous in vitro study suggested that guaraná could have antitumor action against the breast cancer as well as increase anti-proliferative sensitivity of eight different drugs. However, there are two questions have not yet been clarified: whether this same effect occur in the CRC and which would be the causal mechanism that guaraná act in tumoral cells. There are many biologics proprieties of guaraná published in the literature. Considering that, guaraná could present the antitumor activity by modulations in the Mammalian Target of Rapamycin (mTOR) and Mitogen-activated Protein Kinase (MAPKs) pathways. Objective: the aim of this study was to analyze the antitumor in vitro effect of the hydroalcoholic guaraná end its main bioactives molecules in the CRC and in the breast cancer cells. The action in the chemotherapic activity of this extract also was investigated in the CRC cells. Besides, the cytotoxicity of guaraná was analyzed in the healthy cells. Methods: The study was performed using two cell lines HT-29 and MCF-7, CRC and breast cancer, respectively. The cell line HT-29 was exposed to different concentrations of guaraná, as well as its main bioactive molecules, caffeine, theobromine and catechin. Guaraná effect in chemotherapy activity was measured by HT-29 exposure to the better antitumor guaraná concentrations, besides its bioactive compounds in the addiction of Oxaliplatin. Although, the cell line MCF-7 was exposed to different concentrations of guaraná and only the molecule more prevalent found in the extract, the caffeine. Some parameters were analyzed, such as cellular proliferation and viability, cell cycle arrests, apoptotic pathway activation, cancer association proteins expression, modulations in mTOR and MAPKs pathways. These parameters were measured by spectrophotometric, fluorimetric and molecular analysis. Moreover, cytotoxicity parameters of the extract were performed in healthy cells, using fibroblast lineage (HFF-1) and peripheral blood mononuclear cells (PBMCs). Results: Guaraná exhibited antitumor activity in some concentrations (0.1; 1; 10; 30; 100 e 300 μg/mL), as well as its bioactive compounds in the both cell linage tested, HT-29 and MCF-7. Besides, the action of Oxaliplatin was potentiated in some concentrations of guaraná (30; 100 e 300 μg/mL) and its bioactive molecules on HT-29. The guaraná did not negatively interfere in the action of Oxaliplatin. Guaraná and caffeine inhibited proteins in MAPKs and mTOR pathways on MCF-7. However, the guaraná only inhibited the mTOR pathway and the caffeine did not present effect. The guaraná did not present cytotoxic effect on healthy cells. Therefore, the results suggested that the guaraná could be a potential carcinogenic agent besides it could be used as a supplement during the chemotherapic treatment for potentiating the antitumor response and decrease the tumor cells resistance.