Glyphosate induces epithelial mesenchymal transition related changes via estrogen 2 receptor pathway.

GASTIAZORO MP; VARAYOUD J; ZIERAU, OLIVER

Simposio; International Research Alumni Symposium. Efficacy and safety of the use of natural compounds ? progress through ?omics? technologies and CRISPR/Cas; 2019

The safety, including the endocrine disruptive capability and the role on cancer related process, of glyphosate is a matter of intense global debate. We evaluated the possible effects on epithelial mesenchymal transition (EMT) related process exerts by glyphosate (Gly) and the potential endocrine disruptor effect of glyphosate in this process. In this study, we examined whether glyphosate can induce EMT related changes on human endometrial carcinoma cell line (Ishikawa cells) and if glyphosate use the estrogen receptor pathway. Ishikawa cells exposed to a reference dose of pure glyphosate, in an interval of concentrations from 0.2 µM to 200 µM including the reference dose (RfD),showed a reduction in cell viability and an increase on cell migration and invasionability compared to vehicle, as did 17β-estradiol (E2). In addition, we detected a down regulation of E-cadherin mRNA expression of Ishikawa cells in response to the application of glyphosate and E2. Taken together, these results show the properties of glyphosate to promote EMT related changes. Besides, we evaluated if glyphosate, acting as a possible endocrine disruptor, could produce its effects via estrogen receptor pathway. The addition of inhibitor of ER (ICI 182,780) abolishes all the changes provoked by Gly mentioned above. Thus, these results indicate that glyphosate could promote the EMT related changes via ER pathway. Our study contributes to the existing knowledge about in vitro exposure to glyphosate and the effect related with endometrial cancer process. In addition, we provide a new insight in relation to ER mediated effect by glyphosate action.