Citotoxicidade do extrato clorofórmico e do ácido betulínico de eremanthus erythropappus a células tumorais mamárias

Abstract

Breast Cancer is the most commonly diagnosed malignant tumor worldwide, surpassing cases of lung cancer. Despite scientific advances, it remains the second cause of death in women, questioning current treatment methods and requiring dedicated efforts to characterize new drugs. Natural products stand out, since they have active compounds with broad antitumor action, interfering with different oncogenic pathways. The present study aimed to determine the in vitro activity of the chloroform extract of Eremanthus erythropappus and betulinic acid obtained from this species in breast cancer cell lines. Four cell lines, MCF-10A (non-tumorigenic), MCF7 (luminal tumor), MDA-MB-453 (HER2-positive tumor) and MDA-MB-231 (triple-negative tumor) were cultured and treated with different concentrations (7 µg/mL at 500 µg/mL) of EAT21 (chloroform extract) and EAT22 (betulinic acid). Cytotoxicity was evaluated by the standard method using MTT, the IC50 (capacity to inhibit 50% of cells) calculated and selectivity defined. Antiproliferative activity was also determined by clonogenic assay, using the triple negative cell line MDA-MB-231. Both EAT21 and EAT22 were active in MCF7 and MDA-MB-231 cells. However, the luminal breast cancer line was more sensitive, with IC50 below the lowest concentration for both compounds and after treatments for 24 and 48h. For MDA-MB-231, EAT22 stood out, with IC50 < 7 µg/mL after 24 h and 48 h. This compound also significantly inhibited the clonogenicity of triple-negative breast cancer cells. Our results direct in-depth studies in animal models and the mechanisms of action of betulinic acid as a possible therapeutic alternative for the treatment of triple-negative breast cancer.