Integrated network toxicology, molecular docking, and molecular dynamics simulation reveals mechanisms of benzo[a]pyrene-induced pan-cancer

BACKGROUND: Benzo[a]pyrene (B[a]P), a ubiquitous environmental pollutant, is prevalent in emissions, food products, and tobacco. Although B[a]P’s carcinogenicity is well-established, the common molecular mechanisms underlying its pan-cancer carcinogenesis remain incompletely understood. This study systematically investigated B[a]P’s shared pathogenic mechanisms in 10 common solid tumors: bladder, breast, cervical, colorectal, esophageal, gastric, liver, lung, prostatic, and thyroid cancer. METHODS: Computational tools assessed B[a]P toxicity and identified targets. Disease targets for each cancer were retrieved from databases. Intersection analysis found candidate targets. Core targets were identified via protein-protein interaction network. GO/KEGG analyses revealed biological roles and pathways. The binding performance of B[a]P to the core targets was analyzed using molecular docking and molecular dynamics simulations. RESULTS: Cancer-specific potential toxicity targets were identified (range: n = 40–59). Enrichment analysis revealed conserved carcinogenic pathways across cancer types, including cellular response to xenobiotic stimuli, chemical carcinogen-induced receptor activation and DNA adduct formation, cytochrome P450-mediated xenobiotic metabolism, endocrine resistance, steroid hydroxylase activity, and calcium signaling pathways. Common core targets included ESR1, EGFR, MAPK3, MMP9, and PTGS2. Molecular docking and dynamics simulations confirmed strong B[a]P binding to these targets. CONCLUSION: This study elucidated fundamental molecular features of B[a]P-induced pan-carcinogenesis, providing a theoretical framework for developing universal prevention and therapeutic strategies.