Endocrine Disruptors and Endometrial Cancer: Molecular Mechanisms of Action and Clinical Implications, a Systematic Review

Abstract

It has been widely demonstrated that endocrine disruptors play a central role in various physiopathological processes of human health. In the literature, various carcinogenic processes have been associated with endocrine disruptors. A review of the molecular mechanisms underlying the interaction between endocrine disruptors and the endometrial cancer has been poorly developed. A systematic review was performed using PubMed^®/MEDLINE. A total of 25 in vivo and in vitro works were selected. Numerous endocrine disruptors were analyzed. The most relevant results showed how Bisphenol A (BPA) interacts with the carcinogenesis process on several levels. It has been demonstrated how BPA can interact with hormonal receptors and with different transcription proliferative and antiproliferative factors. Furthermore, the effect of Polycyclic aromatic hydrocarbons on Aryl hydrocarbon receptors was investigated, and the role of flame retardants in promoting proliferation and metastasis was confirmed. The results obtained demonstrate how the mechanisms of action of endocrine disruptors are manifold in the pathophysiology of endometrial cancer, acting on different levels of the cancerogenesis process.

Keywords: Alkylphenol Ethoxylates; Flame Retards; Organoclorurate; Polycyclic aromatic; bisphenol A; cadmium; endocrine disruptors; endometrial cancer; mycotoxins.

Figure 1

EDCs and EC. Bisphenol A:BPA; E: Estrogen; P:progesteron; fibroblast growth factor receptor: FGFr; Extracellular signal-regulated protein kinases 1 and 2: ERK1/2; Heart- and neural crest derivatives-expressed protein 2:HAND2; epithelial-mesenchymal transition: EMT; cyclooxygenase-2:COX-2; MicroRNAs:miRNAs; increased nuclear translocation of estrogen-related receptor γ (ERRγ); Polycyclic aromatic hydrocarbons: PAHs; aryl hydrocarbon receptor:AhR; poly-glutamine polymorphism: AR-Q; benzo(a)pyrene: BaP; Halogenated flame retardants:HFRs; Ethoxylated alkylene: APEOS; zearalenone:ZEN; Polychlorinated Biphenyls: PCB; p,p’-dichlorodiphenyldichloroethylene: p,p’V-DDE: superoxide dismutase 1:SOD1; red cross: iterferes.