Objective: The objective of this study was to elucidate the molecular mechanisms underlying the potential contribution of commonly utilized plasticizers, including Diethyl phthalate (DEP), Dimethyl phthalate (DMP), and Dioctyl phthalate (DOP), to the pathogenesis of breast cancer. This study aimed to highlight the complex interactions between these environmental chemicals and key molecular pathways implicated in tumorigenesis.
Methods: We employed network toxicology and molecular docking techniques to analyze the interactions between plasticizers and key proteins implicated in breast cancer. Utilizing databases such as the TCGA, we performed an expression analysis of selected key genes in breast cancer tissue compared to normal controls. Enrichment analysis was conducted to identify the biological pathways associated with these genes.
Results: Enrichment analysis highlighted the association of these plasticizer-targeted genes with pathways integral to adenocarcinoma development, suggesting a broad impact of plasticizers on hormone-dependent and other forms of cancers. Subsequent expression analysis using data from the TCGA breast cancer database indicated significant upregulation or downregulation of these genes in breast cancer tissues compared to normal controls, confirming their pivotal roles in tumor biology. Furthermore, the molecular docking analysis revealed that plasticizers, including DEP, DMP, and DOP, exhibit specific binding interactions with key proteins such as MAPK1, AKT1, SRC, ESR1, and ALB, which are crucial in the regulation of breast cancer pathogenesis.
Conclusion: The study provides evidence that exposure to plasticizers may influence breast cancer pathogenesis through interactions with critical proteins and signaling pathways. By employing network pharmacology, protein interactions, and molecular docking, our findings highlight the potential risks posed by plasticizers. These results underscore the need for further epidemiological and clinical research to fully understand the implications of plasticizer exposure on breast cancer risk, thus informing future preventive and therapeutic strategies.
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http://dx.doi.org/10.1016/j.ecoenv.2024.116866 | DOI Listing |
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