ESTUDO DA ATIVIDADE ANTITUMORAL DE FLAVONOIDES BRACHYDINAS EM LINHAGENS DE CÂNCER DE MAMA

Abstract

Fridericia platyphylla is a shrub native to the Brazilian Cerrado and with great antiproliferative potential, according to scientific literature. Around the world, breast cancer kills thousands of women every year and one of its main problems is the lack of affordable treatments. The objective of this work was to investigate the antitumor activity of Brachydins A and C against different breast cancer cell lines (MCF7 - hormone responsive mammary adenocarcinoma and MDA-MB-231 - triple negative breast adenocarcinoma) and in non-tumor cell line GM 07492A - non-tumor lung fibroblast). The methodology involved in silico analysis of prediction, Linpiski's rule and target receptors. The in vitro study consisted of cytotoxicity assays, cell migration, cell cycle, morphology, apoptosis and caspases. The in silico approach revealed that Brachydinas meet the chemical characteristics relevant for drug prototypes. The in silico prediction indicated that Brachydinas have a great possibility of interacting with the hypoxia-inducible factor (HIF 2α) and androgenic receptor. The IC50 concentrations obtained for Brachydinas A and C varied between 4.62 and 6.00 µg/mL for the three strains. In the cell migration assay, the flavonoids Br-A and Br-C showed a low capacity to inhibit cell migration in MCF-7, in MDA-MB-231 did not cause significant interference. Based on in silico, viability and migration assays, the effect of Brachydinas on death mechanisms was studied in the positive estrogen receptor lineage (MCF-7). Morphological analysis revealed typical changes of the apoptotic process, such as reduction in cell volume, loss of adhesion and presence of condensed nuclei and apoptotic bodies in MCF-7 and GM 07492A. Brachydinas A and C demonstrated a strong pro-apoptotic effect, with death in more than 90% of MCF-7 and GM 07492A cells in the first 24 hours of treatment, with no effect on the cell cycle. The immunofluorescence assay revealed the activation of caspases in MCF-7 and GM. In summary, Brachydins A and C have remarkable antiproliferative and pro-apoptotic potential in breast cancer cells, suggesting that these flavonoids can be exploited in the development of anticancer therapies.