Unveiling curcumin’s therapeutic potential against hepatocellular carcinoma: a multi-pronged approach using network pharmacology, molecular docking, and dynamics simulation

Abstract

Hepatocellular carcinoma is one of the most lethal malignancies which is a rapidly growing and aggressive cancer of the liver. It ranks as the third most common cause of cancer-related death and the sixth most common tumor. The herb Curcuma longa contains a hydrophobic polyphenol called curcumin, which possesses a diverse range of biological and pharmacological properties, including anti-inflammatory, anti-oxidant, anti-proliferative, and antiangiogenic activities. Despite these known effects, the specific molecular mechanism by which curcumin exerts its anti-cancer effects on HCC-related targets through network pharmacology has yet to be fully understood. In this study, To assess the drug-like properties and ADME characteristics of curcumin, the QikProp tool in the Maestro module of Schrödinger software was utilized. Further we identified a total of 407 potential targets that overlapped between HCC and curcumin through network pharmacology approch. To gain further insights into these targets, we conducted gene ontology, and pathway enrichment analyses using the Enrichr webserver. Additionally, we constructed a protein-protein interaction network using Cytoscape software and identified the top 10 hub nodes using the CytoNCA plugin. To validate the significance of these hub nodes, we performed survival analysis using the KM plotter database and expression analysis using the GEPIA2 database. The results obtained from Molecular Docking and Molecular dynamic simulations, conducted using the Glide module and Desmond module respectively (Schrödinger software), and identified TNF as potential target for curcumin in the treatment of HCC. Furthermore, the Prime module in the Schrödinger suite was employed to compute the free energy of binding between curcumin and the protein target, employing the MM/GBSA (Molecular Mechanics/Generalized Born Surface Area) procedure. This analysis revealed a strong binding affinity between TNF and curcumin. Our findings not only support the anti-oncogenic role of curcumin but also shed light on the potential clinical application of curcumin in HCC therapeutics, with TNF as a promising target.

Keywords

HepatoCellular carcinoma / Curcumin / Network pharmacology / Molecular docking and molecular dynamic simulation

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Shenzhen University School of Medicine; Fondazione Istituto FIRC di Oncologia Molecolare