Comprehensive Network pharmacology and in vitro investigation of L-mimosine: unveiling multi-targeted therapeutic potential against breast cancer.

Abstract

Breast cancer remains the leading cause of mortality among women globally, primarily due to its heterogeneity and complex pathophysiology. Conventional treatments such as surgery, radiation therapy, and chemotherapy often face limitations, including significant side effects and the development of drug resistance. Consequently, there is an urgent need to identify novel, effective natural compounds with anti-tumor properties. L-mimosine, a non-protein amino acid derived from the seeds of Leucaena leucocephala and Mimosa pudica, has demonstrated cytotoxic activity against various cancers, including sarcoma, melanoma, breast cancer, and lung cancer. However, its precise molecular mechanisms remain poorly understood. To elucidate these mechanisms, a network pharmacology approach was employed, complemented by molecular docking, molecular dynamics simulations, and in vitro experiments to evaluate the impact of L-mimosine on breast cancer cell proliferation. Breast cancer-associated targets and L-mimosine-interacting genes were retrieved from multiple databases. Pharmacokinetic and toxicity properties were assessed through ADMET analysis. Protein-protein interaction networks of overlapping genes were constructed, identifying key hub genes such as SRC, MAPK8, PRKACA, and AKT1. Among these, AKT1 demonstrated the highest docking scores in molecular docking studies, and molecular simulations confirmed the stability of L-mimosine binding to AKT1. In vitro assays validated that L-mimosine inhibits breast cancer cell proliferation by inducing DNA damage and apoptosis in a dose-dependent manner. Furthermore, L-mimosine was found to arrest MCF-7 cells in the S phase of the cell cycle, as analyzed through cell cycle assays. This research highlights L-mimosine's potential as a promising anticancer agent against breast cancer by promoting apoptosis and interfering with cancer cell cycle progression.