Caracterização das atividades biológicas e das vias oncogênicas moduladas por novos compostos da classe dos benzotiazóis em células tumorais mamárias

Abstract

Breast cancer is the most frequently diagnosed malignancy among women worldwide, with triple-negative breast cancer representing the most aggressive and therapeutically challenging molecular subtype. TNBC lacks the expression of hormone receptors and human epidermal growth factor receptor 2, limiting treatment options primarily to chemotherapy and radiotherapy. However, the effectiveness of these therapies remains limited, highlighting the need for the development of new therapeutic strategies. In this context, benzothiazole derivatives have attracted increasing interest due to their diverse biological properties, including anti-inflammatory activity. This study aimed to evaluate the potential of eight benzothiazole-derived compounds to control breast cancer cells. The non-tumor cell lines HFF (fibroblasts) and MCF-10A (mammary epithelial cells), as well as the tumor cell lines MCF-7 (luminal breast cancer) and MDA-MB-231 (triple-negative breast cancer), were cultured and treated with the eight compounds at different concentrations. Initially, an MTT assay was performed as a screening strategy to identify the compound with the greatest antitumor potential. Based on the results, compound 3 exhibited the highest cytotoxic activity, with an IC50 of 19.34 µM after 48 h of treatment of MDA-MB-231 cells, in addition to significant selectivity (SI > 2). Therefore, subsequent clonogenic, wound healing, and quantitative PCR (qPCR) assays were performed exclusively with compound 3 at concentrations of 9.67 µM (IC50/2) and 4.84 µM (IC50/4) for 48 h. Treatment with compound 3 inhibited clonogenicity and cell migration. Furthermore, qPCR analysis revealed changes in the expression of IL1β, TGFβ, and CDH1, indicating the potential of compound 3 to interfere with processes associated with epithelial-mesenchymal transition. These findings demonstrate the potential of benzothiazole derivatives as anticancer agents, particularly compound 3 as a promising candidate for the treatment of triple-negative breast cancer. Nevertheless, further studies are required to elucidate its mechanisms of action and validate its efficacy in preclinical models.