Network Pharmacology and Molecular Docking Identify Medicarpin as a Potent CASP3 and ESR1 Binder Driving Apoptotic and Hormone-Dependent Anticancer Activity
Issued Date
2025-12-23
Resource Type
eISSN
14220067
Scopus ID
2-s2.0-105027032471
Pubmed ID
41516052
Journal Title
International Journal of Molecular Sciences
Volume
27
Issue
1
Rights Holder(s)
SCOPUS
Bibliographic Citation
International Journal of Molecular Sciences Vol.27 No.1 (2025)
Suggested Citation
Rattanapan Y., Sitthirak S., Tedasen A., Duangchan T., Dokduang H., Pattaranggoon N.C., Saisuwan K., Chareonsirisuthigul T. Network Pharmacology and Molecular Docking Identify Medicarpin as a Potent CASP3 and ESR1 Binder Driving Apoptotic and Hormone-Dependent Anticancer Activity. International Journal of Molecular Sciences Vol.27 No.1 (2025). doi:10.3390/ijms27010174 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/114041
Title
Network Pharmacology and Molecular Docking Identify Medicarpin as a Potent CASP3 and ESR1 Binder Driving Apoptotic and Hormone-Dependent Anticancer Activity
Corresponding Author(s)
Other Contributor(s)
Abstract
Ovarian cancer (OC) remains one of the most lethal gynecologic malignancies due to late diagnosis, rapid progression, and frequent chemoresistance. Despite advances in targeted therapy, durable responses are uncommon, underscoring the need for novel multitarget agents capable of modulating key oncogenic networks. Medicarpin, a natural pterocarpan phytoalexin, exhibits diverse pharmacological activities; however, its molecular mechanisms in OC are poorly defined. This study employed an integrative in silico framework combining network pharmacology, pathway enrichment, molecular docking, and survival analysis to elucidate medicarpin's therapeutic landscape in OC. A total of 107 overlapping targets were identified, resulting in a dense protein-protein interaction network enriched in kinase-mediated and apoptotic signaling pathways. Ten hub genes were emphasized: CASP3, ESR1, mTOR, PIK3CA, CCND1, GSK3B, CDK4, PARP1, CHEK1, and ABL1. Gene Ontology and KEGG analyses demonstrated substantial enrichment in the PI3K-Akt/mTOR and prolactin signaling pathways. Docking revealed the stable binding of medicarpin to CASP3 (-6.13 kcal/mol) and ESR1 (-7.68 kcal/mol), supporting its dual regulation of hormonal and apoptotic processes. Although CASP3 and ESR1 expression alone lacked prognostic significance, their network interplay suggests synergistic relevance. Medicarpin exhibits multitarget anticancer potential in OC by modulating kinase-driven and hormone-dependent pathways, warranting further experimental validation.