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.

Acknowledgments

The authors thankful to the Mrs. Fatima Rafiq Zakaria, Chairman Maulana Azad Educational Trust, Dr. Rafiq Zakaria Campus, Aurangabad 431001(MS), India for providing the laboratory facility and Aakaar Biotechnologies Pvt. Ltd. Lucknow, UP, India for in-vitro experimental activity. This work was supported by the Department of Science and Technology (DST), New Delhi, India [Project File No. EEQ/2016/00055].

Conflict of Interest

The authors confirm that this article content has no conflict of interest.

Funding

This research received no grant from any funding agency.

Author Contribution

All the authors contributed equally. Nikhil S. Sakle and Santosh N. Mokale conducted experimental design and manuscript written. Shweta A. More conducted network pharmacology analysis. All authors reviewed manuscript for the submission.

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.