Investigating the mechanism of action of grape active compounds in treating non-small cell lung cancer (NSCLC) through a network pharmacology and molecular docking approach

Abstract

Although Vitis vinifera is a major fruit crop with well-established nutritional and therapeutic qualities, little is known about its possible anti-cancer benefits. This study examined the mechanisms of action in the treatment of non-small cell lung cancer (NSCLC) using a network pharmacology and molecular docking method. A total of 456 potential protein targets were obtained from the identification of ten major bioactive chemicals, including ascorbic acid, citric acid, succinic acid, caffeic acid, and chlorogenic acid. 149 genes overlapped when 5,941 NSCLC-related targets from GeneCards were integrated. The protein-protein interaction (PPI) network analysis identified ten key hub proteins (e.g., EGFR, ESR1, CASP3), with interaction scores ranging from 73 to 53. Molecular docking revealed strong binding affinities between key compounds and hub proteins, most notably citric acid and EGFR (-10.75 kcal/mol) and chlorogenic acid and ESR1 (-6.85 kcal/mol). Stability was further supported by the presence of 2 to 7 hydrogen bonds in each complex. Survival analysis indicated that PTGS2 overexpression significantly correlates with poor prognosis (p = 0.029). Significant participation in cell proliferation, apoptosis control, inflammatory pathways, and cancer-related signalling cascades was shown by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment studies. Strong binding affinities between important chemicals and hub proteins were shown by molecular docking, indicating that these compounds may have a pharmacological effect. GEPIA-based survival study revealed an overexpression of major oncotargets and the association between PTGS2 expression and overall survival of patients with NSCLC. These results establish a basis for additional experimental validation and medication development while offering molecular insights into V. vinifera's anti-NSCLC potential.

Keywords

• Grape
• Anticancer; Protein-protein interaction
• Caffeic acid
• Chlorogenic acid

References

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