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image of Unravelling the Mechanism of Methylophiopogonanone A Against Esophageal Squamous Cell Carcinoma Based on Network Pharmacology and Molecular Docking
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Abstract

Introduction

Esophageal squamous cell carcinoma (ESCC) stands as one of the deadliest cancers globally. Given the urgent clinical need for more precise and comprehensive therapeutic strategies, the phytocompound methylophiopogonanone A (MO-A) demonstrates the potential as a candidate for ESCC treatment. This study aimed to verify the therapeutic effect of MO-A against ESCC and unveil its underlying mechanism.

Methods

Three compound-protein interaction databases were utilized to predict the molecular targets of MO-A. Subsequently, potential therapeutic targets of ESCC were identified based on the GEO database. KEGG pathway and GO function enrichment analyses were then performed by using these two sets of targets, respectively. Through the integrative analysis of these two target sets, core targets of MO-A with therapeutic potential against ESCC were determined. Protein-protein interaction network analyses and molecular dockings were executed by using these targets. Two human-derived ESCC cell lines were enrolled for biological validation, including cell viability, colony formation, and cell cycle assays.

Results

This study predicted 200 potential targets of MO-A and uncovered 138 key targets associated with the progression of ESCC. Enrichment analyses and PPI networks underscored the involvement of cell cycle-related genes in ESCC development. Four proteins were determined as core MO-A targets for ESCC treatment, including AURKA, AURKB, CDC25B, and TOP2A, which partake in the regulation of the cell cycle. Finally, the inhibitory effect of MO-A on ESCC cell proliferation was validated , primarily through inducing cell cycle arrest at the G2/M phase in ESCC cells.

Discussion

These results revealed the anti-ESCC potential of MO-A, a plant-derived flavonoid, using integrated bioinformatics and biological experiments. While findings provide a mechanistic basis for the efficacy of MO-A, limitations include reliance on computational and models. Further studies should be conducted to evaluate the pharmacological properties and safety of MO-A across multiple models, alongside more comprehensive structure-activity relationship studies to inform drug optimization prior to clinical translation.

Conclusion

MO-A can impede ESCC growth by triggering cell cycle G2/M arrest, positioning it as a novel and promising phytocompound for ESCC therapy.

© 2025 The Author(s). Published by Bentham Science Publishers.
This is an open access article published under CC BY 4.0 https://creativecommons.org/licenses/by/4.0/legalcode
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2025-09-25
2025-12-13

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Unravelling the Mechanism of Methylophiopogonanone A Against Esophageal Squamous Cell Carcinoma Based on Network Pharmacology and Molecular Docking
Bentham Science Publishers ; https://doi.org/10.2174/0115680096387327250906212020
/content/journals/ccdt/10.2174/0115680096387327250906212020
/content/journals/ccdt/10.2174/0115680096387327250906212020
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  • Article Type:     Research Article
Keywords: molecular docking ; network pharmacology ; AURKA ; esophageal squamous cell carcinoma ; Methylophiopogonanone A ; cell cycle ; AURKB

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