Elucidating the potential mechanism of short-chain chlorinated paraffins in breast cancer via computational prediction integrating network toxicology and molecular docking.

Short-chain chlorinated paraffins (SCCPs) are industrial chemicals widely used as plasticizers and flame retardants. Due to their environmental persistence and potential toxicity, understanding their health risks is crucial. The present work aimed to explore the potential link between SCCPs and tumorigenesis by examining the interactions between key molecular pathways through a network toxicological approach. Following the acquisition of the SCCPs structure from the PubChem database, ProTox-II, and ADMETlab2.0 were employed to evaluate the toxicity of SCCPs. Thereafter, network toxicology, molecular docking technology, and molecular dynamics simulation were conducted to analyze the interactions between SCCPs and breast cancer-related proteins. This study investigated the expression levels of screened key genes in breast cancer tissues relative to non-carcinoma samples using databases including TCGA and identified the protein targets in breast cancer associated with SCCPs. The study identified 140 SCCPs-related breast cancer targets. PPI network analysis revealed 8 key targets, including PTGS2 and MMP9. The findings uncovered significant GO terms, comprising 647 biological processes, 24 cellular components, and 63 molecular functions ms, which were predominantly associated with oxidative stress, cellular response to peptide, and endopeptidase activity. KEGG analysis indicated a significant enrichment in the TNF, HIF-1, sphingolipid, and estrogen pathways. Molecular docking and molecular dynamics simulation results showed strong binding interactions between PTGS2, MMP9, and SCCPs. Subsequently, TCGA-breast cancer data-based expression profiling revealed that these genes exhibited significant upregulation or downregulation in breast cancer tissue compared to their non-carcinoma counterparts. These results confirmed their importance in tumor biology. These proteins exert essential effects in regulating breast cancer pathology. This research indicates that SCCPs exposure probably affects the pathogenesis of breast cancer development by interacting with key proteins and relevant pathways. This study utilizes network toxicology, protein interactions analysis, molecular docking, and molecular dynamics simulations to highlight the possible risks associated with SCCPs exposure. These findings contribute to the understanding, prevention of related diseases.