Computational screening of agricultural pesticides for estrogenic activity and Breast cancer risk

Abstract Breast cancer is a leading cause of cancer morbidity and mortality globally, with numerous environmental and genetic factors contributing to its progression. Among environmental factors, exposure to endocrine-disrupting pesticides (EDPs) has garnered significant attention due to their ability to interfere with hormonal pathways, particularly those involving estrogen signalling. This study investigates the molecular docking interactions of widely used pesticides with estrogen receptors ERα, ERβ, and GPER to elucidate their potential role as an endocrine-disrupting pesticide (EDP) in breast cancer. Cyahlothrin is widely used synthetic pyrethroid pesticides among others.The docking analysis revealed strong binding affinities of Cyhalothrin with ERα (-8.6 kcal/mol), ERβ (-11.0 kcal/mol), and GPER (-11.8 kcal/mol). Compared to other EDPs, the results show that Cyhalothrin exhibits superior receptor-binding properties, emphasizing its role as a potent disruptor of estrogenic pathways. These findings suggest that Cyhalothrin mimics endogenous estrogens, leading to overactivation of ERα, suppression of ERβ, and activation of GPER, disrupting normal estrogen signalling. Understanding the molecular interactions between cyhalothrin and estrogen receptors is crucial for assessing its potential role in breast cancer progression. The study also underlines the critical need for stringent regulatory measures to mitigate exposure to Cyhalothrin and similar pesticides to reduce their impact on breast cancer risk. Furthermore, molecular dynamics simulations confirmed the stability of the Cyhalothrin–ERα complex, while Swiss ADME and ADMET-AI analyses revealed favourable drug-like properties but significant carcinogenic and hepatotoxic tendencies. Swiss Target Prediction, ProTox-3.0, and endocrine-disruption screening through ToxCast/Tox21 validated Cyhalothrin’s interaction with estrogenic and oncogenic pathways, reinforcing its classification as a potent endocrine-disrupting pesticide in breast cancer.