Phytochemical Networks to Gene-Level Validation: A Multimodal Evaluation ofGalium aparine against Oral Squamous Cell Carcinoma

Background

This study investigates the anticancer potential of Galium aparine (G. aparine) against Oral Squamous Cell Carcinoma (OSCC) using an integrated network pharmacology and molecular docking approach.

Materials and Methods

Phytochemicals reported in the G. aparine plant were retrieved from the IMPPAT database. OSCC-related genes were identified from GEO, GeneCards, and DisGeNET datasets using Venn analysis. Protein-Protein Interaction (PPI) networks, hub gene identification, and GO/KEGG enrichment analyses were performed. Drug-likeness, pharmacokinetics, toxicity, and biological activity prediction analyses were performed. Molecular docking was conducted using PyRx and Discovery Studio. Possible mutations in the target proteins were identified using cBioPortal, and the mutant forms were also docked with the selected ligands. Molecular dynamics simulation (10 ns) was carried out for the top ligands against wild-type and mutant targets.

Results

A total of 38 phytochemicals were retrieved, and 17 common OSCC-related targets were identified, with MMP1 and MMP9 emerging as key hub genes. Expression, correlation, and druggability analyses confirmed their relevance as OSCC targets. 13 compounds showed favourable drug-like profiles with predicted antineoplastic activity. Mutation analysis revealed 6% alteration in MMP1 and <1% in MMP9. Docking of wild-type and mutant proteins revealed good binding affinities across 13 compounds. Molecular dynamics simulations demonstrated stable complexes (RMSD < 10 Å) for both wild-type and mutant forms. Wet-lab validation further supported these results, as qPCR analysis in KB cells demonstrated marked down-regulation of MMP1 and MMP9 following treatment.

Conclusion

These findings suggest that the anticancer potential of the G. aparine is attributed to the multitarget activity of its phytochemicals.