Luteolin as a Multitarget Agent against Colorectal Cancer Explored Through Integrative Network Pharmacology, Molecular Docking, and Dynamics Simulations.

Colorectal cancer (CRC) is a leading cause of cancer-related death worldwide. Despite advances in current therapeutic strategies, treatment outcomes remain limited and are associated with adverse effects. Consequently, there is growing interest in bioactive compounds such as Luteolin, which has been linked to anticancer properties. Explore the therapeutic potential of Luteolin in CRC using a network pharmacological approach, molecular docking, and molecular dynamics. CRC targets were obtained from the MalaCards and DisGeNET databases. Luteolin targets were obtained from the Comparative Toxicogenomics and SwissTargetPrediction databases. Eighteen common potential targets were analyzed in DAVID to understand the gene ontology. Subsequently, a protein-protein interaction network was constructed in Cytoscape, and six hub genes were identified. These hub genes were analyzed for immune cell infiltration using the TISIDB database. Subsequently, molecular docking of the proteins with Luteolin was performed in Autodock Vina, and the three complexes with the lowest ΔG values were selected for molecular dynamics analysis using GROMACS. Gene ontology results showed that Luteolin activates apoptosis mechanisms, affects transcription and translation processes, affects the cell nucleus, and dysregulates protein kinase activity. The affected KEGG pathways were estrogen signaling and microRNAs. Notably, TOP1 is associated with B-cell and macrophage infiltration. Finally, molecular docking and molecular dynamics confirm stable interactions between Luteolin and the hub genes. Integrative analysis suggests that Luteolin exerts multi-target anticancer effects in CRC by modulating key signaling pathways and forming stable interactions with target proteins. Molecular docking and dynamics simulations support the stability and affinity of the binding. These findings suggest that Luteolin holds significant anticancer potential and may serve as a promising candidate for further experimental investigations in CRC therapy.