Identification of SRC, AKT1 and MAPK3 as therapeutic targets of apigenin and luteolin in colorectal and colon carcinoma through network pharmacology

Apigenin and luteolin are flavonoids with significant therapeutic potential, attributed to their potent antioxidant, anti-inflammatory, and anticancer properties. This study aims to use network pharmacology to identify common target genes of apigenin and luteolin in colorectal carcinoma (CRC) and colon carcinoma (CC), assess their molecular binding with target genes and elucidate potential mechanisms underlying their anticancer effects. Potential targets for apigenin and luteolin were identified using SwissTargetPrediction, the Comparative Toxicogenomics Database (CTD), and SuperPred. CRC- and CC-associated targets were obtained from DisGeNET, GeneCards, and OMIM. Overlapping targets were identified using a Venn diagram. A protein-protein interaction (PPI) network of these overlapping targets was constructed using the STRING database and analyzed with Cytoscape CytoHubba plugin to identify core targets. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Reactome enrichment analyses were performed on the core targets. Molecular docking was performed using Autodock, and molecular dynamics simulations (MDS) with GROMACS for selected targets. A total of 199 common targets of apigenin and luteolin in CRC and CC were identified, with 26 core targets selected for further analysis. Key pathways associated with these targets included cancer-related and immune-related signaling pathways. Molecular docking and MDS confirmed that apigenin and luteolin revealed stronger binding affinities to SRC compared to AKT1 and MAPK3. AKT1, MAPK3 and SRC were identified as key targets for apigenin and luteolin in CRC and CC. These flavonoids may exert their anticancer effects through distinct regulatory mechanisms on AKT1, MAPK3 and SRC, functioning as inhibitors or modulators. • Apigenin and luteolin are flavonoids with high structural similarities that demonstrate potent anti-cancer effects. • This is the first study to identify the common targets of apigenin and luteolin in colon carcinoma (CC) and colorectal carcinoma (CRC) • Molecular docking and molecular dynamics simulation (MDS) were carried out. • AKT1, MAPK3 and SRC were identified as three most critical core targets of apigenin and luteolin in CC and CRC.