Chlorpyrifos subthreshold exposure induces epithelial-mesenchymal transition in breast cancer cells

LASAGNA, M.; HIELPOS, M.S.; VENTURA, C.; MARDIROSIAN, M.N.; MARTÍN, G.; MIRET, N.; RANDI, A.; NÚÑEZ, M.; COCCA, C.

ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY

ACADEMIC PRESS INC ELSEVIER SCIENCE

Año: 2020 vol. 205

0147-6513

Chlorpyrifos (CPF) is one of the most frequently used pesticides in extensive agriculture around the world and can be incorporated by humans and animals with possible consequences on health. The effects of this pesticide on carcinogenesis are not clear and there is no consensus concerning the risks of this compound. In previous work, we demonstrated that CPF induces proliferation of breast cancer cells both in vivo and in vitro. In this work we investigate whether CPF promotes the epithelial-mesenchymal transition (EMT) in breast cancer cells. Herein, we demonstrate that 50 µM CFP induces invasion in MCF-7 and MDA-MB-231 cells. In addition, 0.05 and 50 µM CPF increases migration in both cell lines. In MCF-7 cells, 0.05 and 50 µM CPF increase the metalloprotease MMP2 expression and decrease E-Cadherin and β-catenin expression diminishing their membrane location. Furthermore, 50 µM CPF induces vimentin expression and Slug nuclear translocation in MCF-7 cells. 0.05 and 50 µM CPF increase MMP2 gelatinolytic activity and expression, decrease β-catenin expression and increase vimentin expression in MDA-MB-231 cells.Inhibition of the oncoprotein c-Src reverses all the effects induced by CPF in MDA-MB-231 but not in MCF-7 indicating that c-Src is a kinase with a crucial role in the cells which growth in an estrogen-independent way. In MCF-7 cells both c-Src and estrogen receptor alpha must be blocked to complete inhibit the CPF-mediated effects. Our results show for first time that the exposure to subthreshold concentrations of CPF promotes the modulation of EMT-molecular markers and pathways. These results, together with the ubiquitous distribution of the pesticide CPF, make it of utmost importance to take measures to minimize the risk of exposure to this compound.