Abstract
Breast cancer is a serious public health problem worldwide. Although current treatments with drugs such as cisplatin and paclitaxel are effective, they are associated with severe adverse effects and the development of drug resistance, which has prompted the search for new therapeutic strategies. In this context, the present study evaluated the anticancer activity of the ethanolic extract of Tabernaemontana catharinensis (EET) on the breast cancer cell lines MCF-7 (hormone-sensitive) and MDA-MB-231 (triple-negative) using 2D and 3D models. The results showed that EET significantly reduced cell viability in both lines, with IC(50) values of 83.06 µg/mL (MCF-7) and 8.3 µg/mL (MDA-MB-231) in 2D and 499.3 µg/mL and 280 µg/mL, respectively, in 3D. In addition, treatment with EET caused cell cycle arrest in the G1 phase, reduced CDK4 activity by 58% and ALDH3A1 activity by 32%, and increased levels of the tumor suppressor protein p53. Significant induction of apoptosis was also observed, evidenced by the activation of caspases -3/7, -8, and -9, along with a decrease in intracellular ATP levels (37% in MCF-7 and 90% in MDA-MB-231), suggesting mitochondrial dysfunction. Finally, EET showed the ability to inhibit cell invasion. Taken together, these results indicate that the ethanolic extract of Tabernaemontana catharinensis has potent antiproliferative, proapoptotic, and antimetastatic activity in breast cancer cells, in both two-dimensional and three-dimensional models. Its effect on various key molecular pathways and its ability to enhance the action of conventional chemotherapeutic agents position it as a promising adjuvant agent in the treatment of breast cancer.