Integrated network pharmacology and cellular assay reveal the biological mechanisms of Limonium sinense (Girard) Kuntze against breast cancer

Background: Limonium Sinense (Girard) Kuntze ( L. sinense ) has been widely used for the treatment of anaemia, bleeding, cancer, and other disorders in Chinese folk medicine. Although L. sinense has shown promising inhibitory effects on breast cancer, the exact mechanism underlying its anticancer properties remains unclear. Methods: The active ingredients of L. sinense were collected from published literature, and the potential targets related to L. sinense were obtained from public databases. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and DisGeNET enrichment analyses were performed to explore the underlying mechanisms. Molecular docking, cellular experiments, and Gene Expression Omnibus (GEO) datasets were employed to further evaluate the findings. Results: A total of 15 active ingredients of L. sinense and their corresponding 389 targets were obtained. Enrichment and network analyses revealed that the biological effects of L. sinense were primarily associated with breast cancer. Apigenin within L. sinense was found to potentially play a key role against cancer. Cellular experiments demonstrated that the L. sinense ethanol extract (LSE) exhibited a significant growth inhibitory effect on multiple breast cancer cell lines in both 2D and 3D cultures. Additionally, analysis of GEO datasets validated the significant enrichment of breast cancer and several cancer-related pathways upon treatment with Apigenin in human breast cancer cells. Conclusion: This study predicts the biological activities of L. sinense and demonstrates the inhibitory effect of LSE on breast cancer cells, highlighting the potential application of L. sinense in cancer treatment.