Efeitos biológicos in vitro de extratos da espécie de Renealmia petasites em células de câncer de mama triplo negativo

Abstract

Breast cancer remains a significant challenge for healthcare systems, especially due to the aggressiveness of the triple-negative subtype, which has mortality rates of 30 to 40% within five years of diagnosis. Although chemotherapy is the primary treatment for these tumors, problems such as tumor resistance limit its effectiveness. Thus, natural products emerge as promising, overcoming not only therapeutic failure but also associated toxicity. This study aimed to evaluate the effect of Renealmia petasites extracts in controlling breast tumor cells. To this end, the MDA-MB-231 (triple-negative breast cancer), MCF-7 (luminal breast cancer), MCF-10A (non-tumorigenic), and HFF (human fibroblast) cell lines were treated with the crude extract of the plant's dried leaf (EAT 25) and its fractions (EAT 39-EAT 44), and different biological responses were evaluated. Cytotoxicity, clonogenicity, migration, and qPCR assays were conducted to quantify IL 6, IL-1β, and TGF-β. The crude extract EAT25 showed a mean inhibitory concentration (IC50) of 123.1 µg/mL in the MDA-MB-231 cell line after 48 hours of treatment, while fractions EAT40 to 43 did not significantly reduce viability (IC50 > 500 µg/mL). Fractions EAT39 and EAT44, with IC50s of 24.81 µg/mL and 47.63 µg/mL and selectivity indices of 2.49 and 3.0, respectively, were used in subsequent experiments. A dose dependent reduction in the migration of the MDA-MB-231 cell line was observed after 24 hours of treatment with EAT 39 and EAT 44, with only EAT 44 inhibiting this behavior after 48 hours. Clonogenicity, also after 48 hours, was inhibited for both fractions. Both EAT 39 and EAT 44 reduced IL6 and IL1-β transcripts. Therefore, the species R.petasites shows promise in controlling triple-negative breast cancer cells, so the purification and characterization of the major components of EAT 39 and EAT 44 are essential for validating their antitumor effects, especially in animal models.