Benth Arrests the Cell Cycle, Induces Apoptosis and Inhibits the Invasion of MCF-7 and MDA-MB-231 Cell Lines in 2D and 3D Models.

Breast cancer is a disease with a high incidence and mortality rate worldwide. There is a growing interest in the search for alternative treatments with a good cytotoxic effect but fewer adverse effects, because paclitaxel and cis-platinum treatments present severe adverse effects. The aim of this study was evaluating the antitumor activity of ethyl acetate extract of Benth (EAB) in breast cancer cell lines. The IC50 of EAB is 49.3 μg/mL and 3.7 μg/mL in 2D and 375 μg/mL and 135 μg/mL in 3D in the MCF-7 and MDA-MB-231 cell lines, respectively. It arrested the cell cycle in the G1 phase and decreased CDK4 activity by 86%, increasing the p53 protein levels. During the in silico analysis, the compounds interacted with the IGF-R1, CDK1, CDK2, TNFR1, MLKL, MMP2, MMP9, E-cadherin and N-cadherin proteins, which are involved in necroptosis, invasion and the cell cycle. It decreased the ATP levels in 3D by 87% at 600 μg/mL in MCF-7 and 99% at 250 μg/mL in MDA-MB-231; induced apoptosis by increasing the activity of caspases-3/7, -8 and -9; inhibited invasion and enhanced the effect of cisplatin and paclitaxel in combination with EAB. The results show the antitumor potential of EAB as a possible adjuvant in breast cancer therapy.