{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T02:47:06Z","timestamp":1783565226004,"version":"3.55.0"},"reference-count":60,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T00:00:00Z","timestamp":1770940800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    Hepatocellular carcinoma (HCC) remains lethal despite multitargeted tyrosine kinase inhibitors and immunotherapy, motivating the repurposing of safe, widely available agents. To delineate the anti-HCC potential of propranolol through an in-silico network pharmacology and molecular structure-based study, 70 intersecting potential anti-HCC targets were retrieved from the SwissTargetPrediction and GeneCards databases. Protein\u2013protein interaction (PPI) analysis identified a network of 64 interconnected nodes exhibiting a high average node degree of 9.84, highlighting target centrality. Subsequent hub analysis isolated nine pivotal proteins (SRC, EGFR, CCND1, JAK2, ERBB2, PARP1, CDK4, CDK2, CHEK1) with degree centrality values exceeding 23.2, more than twice the network average. Gene Ontology and KEGG enrichment analyses underscored robust involvement in oncogenic pathways, including PI3K\u2013Akt, MAPK, and immune checkpoints. Molecular docking revealed strong binding affinities of propranolol toward key kinases, notably JAK2 (\u20138.14 kcalmol\n                    <jats:sup>-1<\/jats:sup>\n                    ), ERBB2 (\u20137.80 kcalmol\n                    <jats:sup>-1<\/jats:sup>\n                    ), EGFR (\u20137.76 kcalmol\n                    <jats:sup>-1<\/jats:sup>\n                    ), and CDK2 (\u20137.44 kcalmol\n                    <jats:sup>-1<\/jats:sup>\n                    ). Molecular dynamics simulations confirmed the complex stability, with RMSD values stably maintained below 4.5 \u00c5 over 100 ns simulations. The sustained hydrogen-bond occupancy ranged from 30% to 68% per trajectory, corroborating stable ligand engagement. Collectively, these factorial results provide compelling evidence that propranolol may interact with core oncogenic kinase cluster and potential modulation of the critical signaling cascades implicated in HCC pathogenesis. Collectively, these computational findings support the hypothesis that propranolol possesses the molecular characteristics of a viable therapeutic candidate for HCC, thereby substantiating the need for rigorous experimental and translational investigation to validate its clinical potential.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0333978","type":"journal-article","created":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T18:27:52Z","timestamp":1771007272000},"page":"e0333978","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["In-silico target prediction and pathway analysis of propranolol as a potential therapeutic agent for hepatocellular 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Llovet","year":"2008","journal-title":"N Engl J Med"},{"key":"pone.0333978.ref008","doi-asserted-by":"crossref","first-page":"752725","DOI":"10.3389\/fonc.2021.752725","article-title":"Improving outcomes of tyrosine kinase inhibitors in hepatocellular carcinoma: new data and ongoing trials","volume":"11","author":"L Mou","year":"2021","journal-title":"Front Oncol"},{"issue":"22","key":"pone.0333978.ref009","doi-asserted-by":"crossref","first-page":"12441","DOI":"10.3390\/ijms252212441","article-title":"Drug repurposing for cancer treatment: a comprehensive review","volume":"25","author":"AH Al Khzem","year":"2024","journal-title":"Int J Mol Sci"},{"issue":"1","key":"pone.0333978.ref010","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1038\/s41392-024-01808-1","article-title":"Drug repurposing for cancer therapy","volume":"9","author":"Y Xia","year":"2024","journal-title":"Signal Transduct Target 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Pasquier","year":"2011","journal-title":"Oncotarget"},{"key":"pone.0333978.ref014","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.vph.2010.08.002","article-title":"Propranolol suppresses angiogenesis in vitro: inhibition of proliferation, migration, and differentiation of endothelial cells","volume":"53","author":"S Lamy","year":"2010","journal-title":"Vascul Pharmacol"},{"issue":"3","key":"pone.0333978.ref015","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1007\/s10238-022-00842-z","article-title":"Beta-adrenergic receptor blockers and hepatocellular carcinoma survival: a systemic review and meta-analysis","volume":"23","author":"H Chang","year":"2023","journal-title":"Clin Exp Med"},{"key":"pone.0333978.ref016","first-page":"680","article-title":"Repurposing Drugs in Oncology (ReDO)-Propranolol as an anti-cancer agent","volume":"10","author":"P Pantziarka","year":"2016","journal-title":"Ecancermedicalscience"},{"issue":"4","key":"pone.0333978.ref017","first-page":"5213","article-title":"Propranolol suppresses the proliferation and induces the apoptosis of liver cancer cells","volume":"17","author":"F Wang","year":"2018","journal-title":"Mol Med Rep"},{"issue":"2","key":"pone.0333978.ref018","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.canlet.2005.08.031","article-title":"Molecular pathways in hepatocellular carcinoma","volume":"240","author":"R Pang","year":"2006","journal-title":"Cancer Lett"},{"issue":"10127","key":"pone.0333978.ref019","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1016\/S0140-6736(18)30010-2","article-title":"Hepatocellular carcinoma","volume":"391","author":"A Forner","year":"2018","journal-title":"Lancet"},{"issue":"1","key":"pone.0333978.ref020","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1186\/s13321-020-00450-7","article-title":"A review of computational 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VENNY. An interactive tool for comparing lists with Venn Diagrams. 2007. http:\/\/bioinfogp.cnb.csic.es\/tools\/venny\/index.html"},{"issue":"1","key":"pone.0333978.ref024","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1093\/nar\/gkg034","article-title":"STRING: a database of predicted functional associations between proteins","volume":"31","author":"C von Mering","year":"2003","journal-title":"Nucleic Acids Res"},{"issue":"18","key":"pone.0333978.ref025","doi-asserted-by":"crossref","first-page":"2347","DOI":"10.1093\/bioinformatics\/btq430","article-title":"Cytoscape Web: an interactive web-based network browser","volume":"26","author":"CT Lopes","year":"2010","journal-title":"Bioinformatics"},{"key":"pone.0333978.ref026","article-title":"DAVID: a web server for functional enrichment analysis and functional annotation of gene lists (2021 update","volume":"50","author":"BT Sherman","year":"2022","journal-title":"). 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gene copy number gain in hepatocellular carcinoma promotes cancer progression through \u03b2-catenin-EGFR-PI3K-Akt-mTOR signaling pathway","volume":"57","author":"B Zhang","year":"2018","journal-title":"Mol Carcinog"},{"issue":"20","key":"pone.0333978.ref039","doi-asserted-by":"crossref","first-page":"3845","DOI":"10.1158\/0008-5472.CAN-21-4140","article-title":"Inhibition of EGFR Overcomes Acquired Lenvatinib Resistance Driven by STAT3-ABCB1 Signaling in Hepatocellular Carcinoma","volume":"82","author":"B Hu","year":"2022","journal-title":"Cancer Res"},{"issue":"2","key":"pone.0333978.ref040","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1002\/mc.10028","article-title":"Polymorphisms in cyclin D1 gene and hepatocellular carcinoma","volume":"33","author":"Y-J Zhang","year":"2002","journal-title":"Mol Carcinog"},{"issue":"15","key":"pone.0333978.ref041","doi-asserted-by":"crossref","first-page":"5769","DOI":"10.18632\/aging.102165","article-title":"The combination of lonafarnib and sorafenib induces cyclin D1 degradation via ATG3-mediated autophagic flux in hepatocellular carcinoma cells","volume":"11","author":"J Wang","year":"2019","journal-title":"Aging (Albany NY)"},{"issue":"22","key":"pone.0333978.ref042","doi-asserted-by":"crossref","first-page":"4191","DOI":"10.1158\/0008-5472.CAN-22-1203","article-title":"MEX3C-mediated decay of SOCS3 mRNA Promotes JAK2\/STAT3 signaling to facilitate metastasis in hepatocellular carcinoma","volume":"82","author":"Y Xiao","year":"2022","journal-title":"Cancer Res"},{"issue":"1","key":"pone.0333978.ref043","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1038\/s41419-025-07558-4","article-title":"CSF3R-AS promotes hepatocellular carcinoma progression and sorafenib resistance through the CSF3R\/JAK2\/STAT3 positive feedback loop","volume":"16","author":"Z Feng","year":"2025","journal-title":"Cell Death 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radioresistance by facilitating CHK1 activation","volume":"39","author":"J Sun","year":"2020","journal-title":"J Exp Clin Cancer Res"},{"issue":"1","key":"pone.0333978.ref053","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1038\/s41392-024-02075-w","article-title":"Hepatocellular carcinoma: signaling pathways and therapeutic advances","volume":"10","author":"J Zheng","year":"2025","journal-title":"Signal Transduct Target Ther"},{"issue":"1","key":"pone.0333978.ref054","doi-asserted-by":"crossref","first-page":"2581","DOI":"10.1038\/s41467-024-46835-2","article-title":"Cancer cell genetics shaping of the tumor microenvironment reveals myeloid cell-centric exploitable vulnerabilities in hepatocellular carcinoma","volume":"15","author":"CFA Ramirez","year":"2024","journal-title":"Nat Commun"},{"issue":"3","key":"pone.0333978.ref055","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1038\/s41416-024-02684-w","article-title":"The association between tumour heterogeneity 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