Differential mechanisms of action are involved in chlorpyrifos effects in estrogen-dependent or -independent breast cancer cells exposed at low or high doses of the pesticide

CLARA VENTURA; MARIEL NÚÑEZ; NOELIA MIRET; DIEGO MARTINEL LAMAS; ANDREA RANDI; ANDRÉS VENTURINO; ELENA RIVERA; CLAUDIA COCCA

TOXICOLOGY LETTERS

ELSEVIER IRELAND LTD

Lugar: Amsterdam; Año: 2012 vol. 213 p. 184 - 193

0378-4274

It has reported that many environmental compounds may display estrogenic actions andthese findings led to researchers to associate breast cancer risk with the use of somepesticides. The aim of this work was to investigate the effect of chlorpyrifos (CPF) on cellproliferation and the ERα-dependence of this action employing MCF-7 and MDA-MB-231breast cancer cell lines. We have also analyzed CPF action on the cell cycle distribution andthe cyclins that are implicated in G1-S and intra-S checkpoints. Finally, the action on celldeath and ROS production were studied. We demonstrated the ability of CPF 0.05 μM toinduce cell proliferation through ERα in hormone-dependent breast cancer cells. Incontrast, CPF 50 μM induces intra-S arrest modifying checkpoints proteins, through amechanism that may involve changes in redox balance in MCF-7. In MDA-MB-231, wehave found that CPF 50 μM produces an arrest in G2/M phase which could be related to thecapacity of the pesticide for binding to tubulin sites altering microtubules polymerization.Altogether, our results provide new evidences on the action of the pesticide CPF as anenvironmental breast cancer risk factor due to the effects that causes on the mechanismsthat modulate breast cell proliferation.