Exploring the toxicological mechanisms of atrazine in prostate cancer by network toxicology and molecular docking

Abstract

Atrazine (ATZ) is the second most used herbicide against broadleaf and grassy weeds worldwide. ATZ persists in soil and water due to its long half-life, and is considered an endocrine disrupting chemical for humans. Epidemiological studies have indicated an intimate relationship between ATZ and the pathogenesis of prostate cancer (PCa). However, the underlying toxicological mechanisms remain barely elucidated. Leveraging the CTD, GeneCards, OMIM, PharmGKB, and TTD databases, we identified 154 target genes associated with ATZ exposure and PCa. Using STRING and Cytoscape tools, a PPI network was constructed, and five key genes involved in ATZ-induced PCa toxicity including TP53, JUN, AKT1, BCL2, and IL1B were extracted. Enrichment analysis of target genes highlighted the association of ATZ with pathways integral to PCa development. Expression analysis, ROC curve analysis, immune correlation analysis, and single-gene GSEA of these key genes confirmed their pivotal role in PCa biology. Furthermore, we employed Autodock Vina for molecular docking analysis, demonstrating strong binding between ATZ and the key genes. Collectively, our findings suggest that ATZ may serve as a potential environmental pollutant influencing the pathogenesis of PCa through interactions with key proteins and signaling pathways, offering a theoretical groundwork for the comprehensive prevention and medical management of PCa patients.

Keywords: Atrazine; Molecular docking; Network toxicology; Prostate cancer.