Multi-Target Inhibition of Hepatocellular Carcinoma via DIBP from Glycyrrhiza uralensis: A Systems Biology and Experimental Approach

Multi-Target Inhibition of Hepatocellular Carcinoma via DIBP from Glycyrrhiza uralensis: A Systems Biology and Experimental Approach | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Multi-Target Inhibition of Hepatocellular Carcinoma via DIBP from Glycyrrhiza uralensis : A Systems Biology and Experimental Approach Imran Ali Khan, Faisal Ali, Bisma Zainab, Azhar Iqbal, Mustapha Belaidi, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7591682/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Hepatocellular carcinoma (HCC) is one of the major causes of cancer-related deaths world wide. Its aggressive nature and late diagnosis imply a very poor survival rate. Therefore there is dire necessity to find new multi-target therapies. In this study, we have identified five veritable hub genes in HCC: CDK1, FOXM1, PTTG1, STMMN1 (overexpressed), and IGFBP3 (downregulated). Through integrated bioinformatics, we have established the clinical relevancy of these five hub genes. The genes are mainly involved in the mitotic processes (e.g. organelle fission, nuclear division, chromosome segregation, etc.), and are over-represented in cell cycle, p53, MAPK, TGF-beta, Hippo signaling. Overexpression of CDK1, FOXM1, PTTG1 and STMN1 is linked with survival and low IGFBP3 to adverse outcomes. The results of immune infiltration showed that the STMN1 level is especially associated with tumor immune cells. Diisobutyl phthalate (DIBP) is one of the bioactive compounds of Gancao, (Glycyrrhiza uralensis Fisch) which we tested by molecular docking, MD simulation, DFT, ADMET prediction, MM/GBSA, and MTT cytotoxicity assays. DIBP binds each hub protein with a stable affinity in silico, exhibits optically favorable drug-like properties and pharmacokinetics, and cause dose-dependent cell death of HCC cell line in in vitro studies. Such in vitro findings compare to the reported selective cell killing of cancer cells by DIBP. In conclusion, the identified hub genes can be used as important diagnostic and prognostic indicators in HCC, and DIBP can serve as a multi-target non-toxic agent against HCC that requires further in vitro research. Bioinformatics Cancer Biology Computational Biology Drug Discovery, Design, & Development Hepatocellular carcinoma Hub genes Bioinformatics analysis Diisobutyl phthalate (DIBP) Multi-target therapy Full Text Additional Declarations The authors declare no competing interests. Supplementary Files FaisalHCCGraphicalAbstract.docx Graphical Abstract SupplementaryFile1.docx Supplementary File 1 SupplementaryFile2.docx Supplementary File 2 Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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