Alysicarpus vaginalis Bio-Actives as ESR Signaling Pathway Inhibitor for Breast Cancer Treatment: A Network Pharmacology Approach

Abstract

In our previous study Alysicarpus vaginalis (AV) has appeared as a promising target for breast cancer hence we have screened potential targets by in silico, In Vitro and In Vivo methods. A network pharmacology (NP) approach involves prediction and validating of targets via molecular modeling, western blotting and In Vivo MNU-induced mammary cancer. The PPI network showed the 573 edges between 214 nodes (targets) that are involved in breast cancer and important one are ESR-1, ESR-2, AR, EGFR, NOS3, MAPK, KDR, SRC and MET. Compound-target-pathway network involves 04 compounds and 221 interactive protein targets associated with breast cancer. GO and KEGG enrichment analysis predicted the ERR, c-MET, PDGFR-α/β, EGFR, and VEGF as a key targets in the breast cancer treatment which are validated via molecular modeling. Expression of ER-α, AR and EGFR were significantly down regulated by AV in MCF-7 cell line. In addition, the immunoreactivity of ER-α was reduced significantly in MNU-induced mammary carcinoma, which is a key target in ER + breast cancer. Overall, this study scientifically light ups the pharmacological mechanism of AV in the treatment of breast cancer, strongly associated with the regulation of ESR signaling pathway.