{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T19:10:37Z","timestamp":1775157037360,"version":"3.50.1"},"reference-count":69,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2024,9,19]],"date-time":"2024-09-19T00:00:00Z","timestamp":1726704000000},"content-version":"vor","delay-in-days":56,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,7,25]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Matairesinol (MAT), a plant lignan renowned for its anticancer properties in hormone-sensitive cancers like breast and prostate cancers, presents a promising yet underexplored avenue in the treatment of metastatic prostate cancer (mPC). To elucidate its specific therapeutic targets and mechanisms, our study adopted an integrative approach, amalgamating network pharmacology (NP), bioinformatics, GeneMANIA-based functional association (GMFA), and experimental validation. By mining online databases, we identified 27 common targets of mPC and MAT, constructing a MAT-mPC protein\u2013protein interaction network via STRING and pinpointing 11 hub targets such as EGFR, AKT1, ERBB2, MET, IGF1, CASP3, HSP90AA1, HIF1A, MMP2, HGF, and MMP9 with CytoHuba. Utilizing DAVID, Gene Ontology (GO) analysis highlighted metastasis-related processes such as epithelial\u2013mesenchymal transition, positive regulation of cell migration, and key Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, including cancer, prostate cancer, PI3K-Akt, and MAPK signaling, while the web resources such as UALCAN and GEPIA2 affirmed the clinical significance of the top 11 hub targets in mPC patient survival analysis and gene expression patterns. Our innovative GMFA enrichment method further enriched network pharmacology findings. Molecular docking analyses demonstrated substantial interactions between MAT and 11 hub targets. Simulation studies confirmed the stable interactions of MAT with selected targets. Experimental validation in PC3 cells, employing quantitative real-time reverse-transcription PCR and various cell-based assays, corroborated MAT\u2019s antimetastatic effects on mPC. Thus, this exhaustive NP analysis, complemented by GMFA, molecular docking, molecular dynamics simulations, and experimental validations, underscores MAT\u2019s multifaceted role in targeting mPC through diverse therapeutic avenues. Nevertheless, comprehensive in vitro validation is imperative to solidify these findings.<\/jats:p>","DOI":"10.1093\/bib\/bbae466","type":"journal-article","created":{"date-parts":[[2024,9,19]],"date-time":"2024-09-19T13:56:13Z","timestamp":1726754173000},"source":"Crossref","is-referenced-by-count":32,"title":["Novel systems biology experimental pipeline reveals matairesinol\u2019s antimetastatic potential in prostate cancer: an integrated approach of network pharmacology, bioinformatics, and experimental validation"],"prefix":"10.1093","volume":"25","author":[{"given":"Rama","family":"Rajadnya","sequence":"first","affiliation":[{"name":"Cancer Biology , Interactive Research School for Health Affairs (IRSHA), , Pune-Satara Road, Dhankawadi, Pune, Maharashtra 411043, India"},{"name":"Bharati Vidyapeeth (Deemed to be University) , Interactive Research School for Health Affairs (IRSHA), , Pune-Satara Road, Dhankawadi, Pune, Maharashtra 411043, India"}]},{"given":"Nidhi","family":"Sharma","sequence":"additional","affiliation":[{"name":"Cancer Biology , Interactive Research School for Health Affairs (IRSHA), , Pune-Satara Road, Dhankawadi, Pune, Maharashtra 411043, India"},{"name":"Bharati Vidyapeeth (Deemed to be University) , Interactive Research School for Health Affairs (IRSHA), , Pune-Satara Road, Dhankawadi, Pune, Maharashtra 411043, India"}]},{"given":"Akanksha","family":"Mahajan","sequence":"additional","affiliation":[{"name":"Cancer Biology , Interactive Research School for Health Affairs (IRSHA), , Pune-Satara Road, Dhankawadi, Pune, Maharashtra 411043, India"},{"name":"Bharati Vidyapeeth (Deemed to be University) , Interactive Research School for Health Affairs (IRSHA), , Pune-Satara Road, Dhankawadi, Pune, Maharashtra 411043, India"}]},{"given":"Amrita","family":"Ulhe","sequence":"additional","affiliation":[{"name":"Cancer Biology , Interactive Research School for Health Affairs (IRSHA), , Pune-Satara Road, Dhankawadi, Pune, Maharashtra 411043, India"},{"name":"Bharati Vidyapeeth (Deemed to be University) , Interactive Research School for Health Affairs (IRSHA), , Pune-Satara Road, Dhankawadi, Pune, Maharashtra 411043, India"}]},{"given":"Rajesh","family":"Patil","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry , Sinhgad Technical Education Society, , Vadgaon (BK), Off Sinhgad Road, Pune, Maharashtra 411041, India"},{"name":"Sinhgad College of Pharmacy , Sinhgad Technical Education Society, , Vadgaon (BK), Off Sinhgad Road, Pune, Maharashtra 411041, India"}]},{"given":"Mahabaleshwar","family":"Hegde","sequence":"additional","affiliation":[{"name":"Innovative Nutrition , Interactive Research School for Health Affairs (IRSHA), , Pune-Satara Road, Dhankawadi, Pune, Maharashtra 411043, India"},{"name":"Bharati Vidyapeeth (Deemed to be University) , Interactive Research School for Health Affairs (IRSHA), , Pune-Satara Road, Dhankawadi, Pune, Maharashtra 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