Elucidation of Therapeutic Mechanism of Lipopeptide Iturin A from Bacillus aryabhattai on Lung Cancer Through Integration of Network Pharmacology, Molecular Docking, Molecular Dynamics Simulation and In Vitro Analysis

Abstract This study used network pharmacology to evaluate iturin A's mechanism of action on lung cancer. Iturin action targets were gathered using the Swiss Target Prediction and PubChem databases. The Gene Cards database was utilised to gather pertinent target sets for lung cancer, and the drug-disease target intersection was identified as a possible site of iturin activity in lungcancer. Using a target protein-protein interaction (PPI) network constructed with the STRING database, topological network analysis was used to identify the primary target genes of iturin A in lung cancer. Subsequently, Cytoscape 3.7.1 was used to import the data. The Shiny database was used to analyse the Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment and Gene Ontology (GO) functional enrichment. Three common targets between lung cancer and iturin A were identified through target intersection. Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA) may be the primary target of iturin activity on lung cancer, according to the PPI map and topological study. According to molecular docking experiments, iturin A had the highest binding affinity to the target. Later, the phosphatidylinositol 4,5-bisphosphate 3-kinase complexed with Iturin A underwent a 200 ns molecular dynamics simulation within a physiological environment. The results illustrated that the ligand maintained a relatively constant shape throughout the simulation. Iturin A was used to treat human lung cancer A549 cells, and the results of the MTT test demonstrated inhibitory action with an IC50 value of 7.73 µM. This allowed for an assessment of the cell's viability. These findings validated iturin-A as an anticancer agent. The combined insights from our network analysis, in-silico tests, and in vitro analyses collectively underscore the potential efficacy of Iturin A in fighting lung cancer.