Avaliação do efeito anticâncer do extrato etanólico de Trichoderma asperelloides em modelo de câncer de mama

Abstract

Cancer is a global disease, with breast cancer being the most common type worldwide (11.7% of cases). The estimated number of new cases of breast cancer in Brazil, for the three-year period from 2023 to 2025, is 73,610, corresponding to an estimated risk of 66.54 new cases per 100,000 women, according to INCA. There is a growing worldwide demand for novel antineoplastic compounds that improve clinical response and decrease relapses, adverse effects and costs. This work evaluated the effect of the ethanolic extract of the fungus Trichoderma asperelloides (ExtTa) on the migration of the breast adenocarcinoma cell lines MDA-MB-231 and 4T1 by the in vitro Wound Healing assay; to evaluate the Acute Oral Toxicity (AOT) by the neutral red test (NRU) according to protocol nº129 of the OECD (Organization for Economic Cooperation and Development) and in vivo test using BALB/c mice and, finally, to analyze the effect of treatment with ExtTa on mice bearing tumors experimentally induced by the injection of 4T1 cells. Results indicated that ExtTa does not interfere with the migration rate of 4T1 and MDA-MB-231 cells, since no difference in the wound healing were found between controls and ExtTa treated cells. The NRU assay showed that ExtTa is cytotoxic to BALB/c 3T3 fibroblast cells and the mean IC50 value found was 55 μg/mL. From this data, the LD50 value found was 471.74 mg/kg and the initial dose was 300 mg/kg defined for the AOT in vivo tests. In vivo AOT tests confirmed ExtTa’s classification in category 4 of the Globally Harmonized System (GHS), as animals treated with a dose of 2,000 mg/kg of ExtTa died, indicating the low potential for acute toxicity. Based on the results found in the evaluation of AOT in vivo, we proceeded with experiments to test, in BALB/c mice carrying breast tumors induced by subcutaneous injection of 4T1 cells, treatment with 5, 15 and 30mg/kg of ExtTa. ExtTa was effective at a dose of 15mg/kg for the treatment of murine breast cancer, despite not exhibiting action on lung metastasis, as well as the standard drug Doxorubicin. However, the ExtTa treatment did not present adverse effects, unlike Doxorubicin. These findings reinforce that ExtTa is a potential anticancer drug.