AVALIAÇÃO DO POTENCIAL ANTITUMORAL DE SELÊNIOCOMPOSTOS EM MODELO TRIDIMENSIONAL DE CÂNCER DE CÓLON IN VITRO

Abstract

Selenium has an important antioxidant function that is related to cellular prevention, cardiac protection, reproduction, metabolic control of hormones, cognitive support, in addition to anti-cancer and anti-inflammatory pharmacological effects. The action of these selenium compounds on metabolic pathways generates the intensification of reactive species to oxygen and nitrogen, which results in increased peroxidation and the reactivity of these metabolic by-products favors cell death events. In this study, the in vitro antiproliferative activity in colon cancer cell lines (Caco-2 and HT-29) cultivated in a monolayer and in a three-dimensional model was analyzed after treatment with concentrations of selenium compounds with an indole core of biological activity and another compound imidazo-pyrimidine, respectively called MRK-104 and MRK-107. Through colorimetric, enzymatic, fluorescence and turbidimetry methodologies, it was possible to identify, evaluate and differentiate several cellular characteristics that permeate the apoptosis and oxidative stress signaling pathway. The antiproliferative responses of selenium compounds in colon cancer lines Caco-2 and HT-29 within 48 hours by the sulforhodamine B colorimetric test show GI50 of 1.1-13 µM, for MRK-104 and MRK-107, of selectively as they did not present an antiproliferative effect on immortalized human fibroblasts (GI50 in HFF1 > 635 µM). Colon cells in the 3D model, labeled with fluorescent DNA agent, at treatment concentrations of GI50 and double the GI50 concentration of selenium compounds at 48 hours induced cell cycle arrest in the G0/G1 phase in both cell lines 72.15% (Caco-2) to 89.12% (HT-29). Furthermore, Se-compounds activate caspase-3 within 24 hours and cause disturbances in redox homeostasis that indicate cell membrane damage and DNA fragmentation by the lipid peroxidation reaction in the TBARS assay. The compounds demonstrated antiproliferative and selective activity, demonstrating potential for continuing studies aimed at anticancer activity.