Journal of Precision Biosciences
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Journal of Precision Biosciences

Volume 6 Number 1 2024

Article Contents

RESEARCH ARTICLE   (Open Access)
Contents Vol 6 (1)

Targeted Drug Repurposing in Precision Oncology Reveals Celecoxib as a GSK-3β Inhibitor in Hepatocellular Carcinoma

Amena Khatun Manica1*, Md Abu Bakar Siddique2, Tufael3, Most Farhana Akter4, Md. Robiul Islam4

+ Author Affiliations

Journal of Precision Biosciences 6 (1) 1-8 https://doi.org/10.25163/biosciences.6110440

Submitted: 10 September 2024 Revised: 29 September 2024  Published: 02 November 2024 

Abstract

Background: Hepatocellular carcinoma (HCC) is a lethal cancer lacking effective targeted therapies. GSK-3β plays a pivotal role in oncogenic signaling in HCC. This study explores the potential of repurposing FDA-approved drugs targeting GSK-3β as a precision medicine approach, aiming to uncover novel therapeutic strategies through in silico molecular modeling.

Aim: This study aimed to identify potential FDA-approved drugs that can be repurposed to inhibit GSK-3β using an in-silico precision medicine approach for HCC.

Methods: The three-dimensional structure of GSK-3β (PDB ID: 1Q3W) was retrieved from the Protein Data Bank and prepared for docking simulations. Four FDA-approved candidate drugs-Celecoxib, Tideglusib, Metformin, and Lithium carbonate-were docked using AutoDock Vina integrated within PyRx. Toxicity profiles were predicted using the ProTox-II webserver. Additionally, functional enrichment and pathway analyses were performed using STRING v11.5 to identify key GO terms and KEGG pathways associated with GSK-3β.

Results: Celecoxib demonstrated the strongest binding affinity and specific hydrophobic and π-sulfur interactions with the GSK-3β active site, suggesting high inhibitory potential. GO and KEGG analyses confirmed GSK-3β’s involvement in cell proliferation, anti-apoptotic regulation, and oxidative stress response. Despite minor predicted toxicities, Celecoxib’s profile was manageable under precision-guided frameworks.

Conclusion: These findings highlight Celecoxib as a promising repurposed candidate targeting GSK-3β in HCC, supporting its potential inclusion in future precision oncology strategies.

Keywords: GSK-3β, Hepatocellular carcinoma (HCC), Drug repurposing, Molecular docking, Celecoxib

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