Anti-breast Cancer Potential of Prosopis cineraria L. Phytocompounds: A Network Pharmacology and in vitro Analysisbased Approach

Background: Prosopis cineraria L. (PCL) is a herbal plant commonly used in Asia for the therapeutic intervention of different kinds of illnesses. Preclinical reports have revealed the beneficial effects of PCL against various types of life-threatening diseases, in-cluding cancer. However, studies targeting breast cancer (BCa) and bioactive for its mecha-nistic approach are limited or not available. Methods: The current work utilized network pharmacology, built a network between plant compounds and BCa targets, and explored the effective phytocompounds of PCL and its possible mode of action. All phytoconstituents of PCL were segregated using the IMPPAT database, and thus, potential phytoconstituents were selected for this study. Phytocom-pounds and BCa target data were entered into Cytoscape software to compose the PCL net-work, and subsequently GO and pathway enrichment analysis were examined. Molecular docking and in vitro experiments were used to further validate the network pharmacology results. Results: We retrieved 24 phytocompounds from PCL and 301 potent BCa-associated targets for network construction, and obtained one main ingredient, luteolin of PCL. MMP9, GSK3Β, PARP1, CYP19A1, MMP2, ABCG2, ESR2, HMGCR, AR, and ABCB1 have been recognized as crucial targets of PCL in BCa treatment. Subsequent in vitro experiments showed that PCL and its final screened constituent, luteolin, inhibited the proliferation of MDA-MB-231 cells and reduced the expression level of MMP9 target genes. Conclusion: Network analysis exhibited that PCL exerted a significant repressive impact on BCa by acting on tumor-associated signaling cascade, which would be helpful for future an-ticancer research of PCL against breast cancer.