Mechanistic decoding of octyl methoxycinnamate-induced breast toxicity via network toxicology, mendelian randomization, and molecular simulations

Abstract

Octyl methoxycinnamate (OMC), a widely used UV filter, has raised concerns due to its potential reproductive toxicity and association with endocrine disruption. This study systematically identified OMC-induced breast toxicity targets and elucidated underlying molecular mechanisms by integrating network toxicology, differential gene expression analysis, Mendelian randomization (MR), molecular docking, and molecular dynamics (MD) simulations. Using SwissTargetPrediction, OMIM, GeneCards and DisGeNET databases, 185 potential targets linked to OMC exposure and breast injury were identified. STRING and Cytoscape analyses highlighted 31 hub targets. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment revealed significant associations with immune responses, cell proliferation, and signaling pathways. Analysis of GEO datasets identified overlapping differentially expressed genes (DEGs) between core targets and breast cancer (BC). MR analysis demonstrated a causal relationship between PTGS2 and BC risk. Molecular docking indicated strong binding affinities between OMC and core targets, particularly MMP9. MD simulations further confirmed stable OMC-PTGS2 interactions, supporting PTGS2 as a key mediator of OMC-induced breast toxicity. This work provides a theoretical foundation for understanding OMC's breast toxicity mechanisms and lays groundwork for preventing or managing breast disorders in populations exposed to OMC-containing environments.

Keywords: Breast injury; Mendelian randomization; Molecular docking; Molecular dynamics simulations; Network toxicology; Octyl methoxycinnamate.