{"title":"Exploring the toxicological mechanisms of atrazine in prostate cancer by network toxicology and molecular docking","authors":"Jinwen Mi , Siyuan Wang, Yifan Hong, Shengde Wu, Guanghui Wei","doi":"10.1016/j.reprotox.2025.109001","DOIUrl":null,"url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"137 ","pages":"Article 109001"},"PeriodicalIF":2.8000,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Reproductive toxicology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0890623825001728","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"REPRODUCTIVE BIOLOGY","Score":null,"Total":0}
引用次数: 0
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.
期刊介绍:
Drawing from a large number of disciplines, Reproductive Toxicology publishes timely, original research on the influence of chemical and physical agents on reproduction. Written by and for obstetricians, pediatricians, embryologists, teratologists, geneticists, toxicologists, andrologists, and others interested in detecting potential reproductive hazards, the journal is a forum for communication among researchers and practitioners. Articles focus on the application of in vitro, animal and clinical research to the practice of clinical medicine.
All aspects of reproduction are within the scope of Reproductive Toxicology, including the formation and maturation of male and female gametes, sexual function, the events surrounding the fusion of gametes and the development of the fertilized ovum, nourishment and transport of the conceptus within the genital tract, implantation, embryogenesis, intrauterine growth, placentation and placental function, parturition, lactation and neonatal survival. Adverse reproductive effects in males will be considered as significant as adverse effects occurring in females. To provide a balanced presentation of approaches, equal emphasis will be given to clinical and animal or in vitro work. Typical end points that will be studied by contributors include infertility, sexual dysfunction, spontaneous abortion, malformations, abnormal histogenesis, stillbirth, intrauterine growth retardation, prematurity, behavioral abnormalities, and perinatal mortality.