Caracterização da ação antitumoral do extrato do fungo Trichoderma asperelloides

Abstract

Cancer is a multifactorial disease that represents one of the main causes of global morbidity and mortality. Lack of response, development of resistance, occurrence of relapses, and adverse effects are frequent problems in the treatment that need to be overcome. The discovery of new antitumor substances for therapeutic alternatives is essential to improve efficacy and specificity, overcome resistance, and allow a more personalized approach. Plants and microorganisms are natural sources of active substances with pharmacological properties. This work aims to evaluate the cytotoxic effect of the crude ethanolic extract of the fungus T. asperelloides (ExtTa) on tumor cell lines and its interaction with chemotherapy drugs. It was observed, by MTT cytotoxicity assay, that ExtTa significantly reduced cell viability in human glioblastoma (T98G), breast cancer (MDA-MB-231), and lung cancer (A549) cell lines, and colorectal carcinoma (HCT116 and WiDr), osteosarcoma (Saos-2), melanoma (LB373) and fibrosarcoma (HT1080). Cytotoxicity was also observed for the 4T1 and SaI/N murine lines of breast adenocarcinoma and fibrosarcoma, respectively. The selectivity index (SI) of the ExtTa is greater to tumor cells is greater than to non-cancer human fibroblast (GM637) and kidney (HEK-293T) cells, and to murine NIH/373 and L929 fibroblasts, the 50% cell inhibitory concentration (IC50) for cells tumor cells was lower than those observed for non-cancer cells. The greatest cytotoxicity and selectivity of ExtTa was found against T98G and HCT116 colorectal glioblastoma cell lines. ExtTa is approximately four times more cytotoxic to these tumor cells than to non-cancer cell lines. Furthermore, when comparing the selectivity index (SI) of doxorubicin (DOX) with that of ExtTa, it was observed that ExtTa was more selective than DOX for all tested cancer lines. The combination of ExtTa treatment with DOX and the 5-Fluorouracil (5-FU) chemotherapy was evaluated. The results showed a potential use for the ExtTa as an adjuvant for these drugs, acting synergistically and allowing dose reduction in osteosarcoma lines Saos-2 and colorectal carcinoma HCT116. The treatment with the ExtTa upmodulated BCL-2 and MAPK1gene expression and promoted cell cycle arrest in the G0-G1 phase. Taken together, our data reveal the existence of bioactive compounds with cytotoxic effects in ExtTa with potential for developing novel anticancer agents.