Novos complexos metálicos de cobre biologicamente ativos em células tumorais mamárias

Abstract

Breast Cancer (BC) is the second most common malignancy among women in Brazil, after non-melanoma skin tumors. Chemotherapy is an important and widely used therapeutic strategy, but resistance and debilitating side effects compromise its effectiveness. Copper metal compounds have stood out for their ability to cleave DNA, to induce reactive oxygen species and promote tumor cell apoptosis, with reduced toxicity. Therefore, the aim of the present study was to evaluate the cytotoxicity of ten new metallic copper compounds and their ligands in the mammary cell lines MCF-10A (non-tumorigenic), MCF7 (BC luminal phenotype) and MDA-MB-231 (BC triple phenotype-negative). The MTT test was adopted in treatments for 24h and 48h with eight concentrations of the complexes. These were not active in the MCF7 strain. For triple-negative BC cells a reduction in their viability was observed, especially after 48 hours. Mi02, Mi05, Mi09 and Mi10 stood out, with IC50 values below 50 µM after 48 hours and reduced by half when compared to 24 hours. The lowest IC50 values were observed for Mi05 and Mi09 with selectivity index (SI) of 2.40 and 3.78, respectively, after 48 hours. Mi05 and Mi09 ligands showed no effect on MCF-10A and MDA-MB-231 lineages after 48 hours. Our results show the promising effect of two new copper metal complexes on triple-negative BC and further studies are needed to investigate the oncogenic pathways modulated by these compounds.