Mechanistic insights into the effects of Tris-2-butoxyethyl phosphate on multiple cancers using network toxicology and molecular docking.

This study investigates the potential mechanisms by which Tris(2-butoxyethyl) phosphate (TBEP) may contribute to the development and progression of human malignancies. Fourteen representative cancer types were selected to explore the molecular pathways through which TBEP may exert its effects. By integrating network toxicology, molecular docking, and molecular dynamics (MD) simulations, we elucidated the underlying mechanisms of TBEP-related carcinogenicity. Potential targets associated with these malignancies were identified using multiple databases, including Public Chemical Database (PubChem), Search Tool for Interacting Chemicals (STITCH), SwissTargetPrediction, The Human Gene Database (GeneCards), the Online Mendelian Inheritance in Man (OMIM), and the Therapeutic Target Database (TTD). Core targets were further screened through STRING analysis and visualized using Cytoscape software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were then performed to characterize the biological functions and pathways involved Three-dimensional structures of the core target proteins were retrieved from the Protein Data Bank (PDB), optimized using PyMOL (version 3.0.3), and subjected to molecular docking with AutoDock Vina to assess their binding affinities with TBEP. The stability of the resulting protein-ligand complexes was validated through MD simulations using GROMACS 2022. Finally, the relevance of the identified cancer types was confirmed using The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases. Overall, our findings suggest that TBEP may promote cancer development by interacting with key targets such as SRC and CASP3 and modulating critical signaling pathways. This study provides new insights into the potential carcinogenic mechanisms of TBEP and offers a theoretical foundation for future prevention and therapeutic strategies.