title: Chlorpyrifos inhibits cell proliferation through ERK1/2 phosphorylation in breast cancer cell lines.
abstract: It is well known the participation of oxidative stress in the induction and development of different pathologies including cancer, diabetes, neurodegeneration and respiratory disorders among others. It has been reported that oxidative stress may be induced by pesticides and it could be the cause of health alteration mediated by pollutants exposure. Large number of registered products containing chlorpyrifos (CPF) is used to control pest worldwide. We have previously reported that 50 μM CPF induces ROS generation and produces cell cycle arrest followed by cell death. The present investigation was designed to identify the pathway involved in CPF-inhibited cell proliferation in MCF-7 and MDA-MB-231 breast cancer cell lines. In addition, we determined if CPF-induced oxidative stress is related to alterations in antioxidant defense system. Finally we studied the molecular mechanisms underlying in the cell proliferation inhibition produced by the pesticide. In this study we demonstrate that CPF (50 μM) induces redox imbalance altering the antioxidant defense system in breast cancer cells. Furthermore, we found that the main mechanism involved in the inhibition of cell proliferation induced by CPF is an increment of p-ERK1/2 levels mediated by H2O2 in breast cancer cells. As PD98059 could not abolish the increment of ROS induced by CPF, we concluded that ERK1/2 phosphorylation is subsequent to ROS production induced by CPF but not the inverse.
authors.affiliation: Laboratorio de Radioisótopos, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Argentina.
authors.forename: Clara
authors.initials: C
authors.lastname: Ventura
authors.affiliation: Laboratorio de Investigaciones Bioquímicas y Químicas del Medio Ambiente (LIBIQUIMA), IDEPA, CONICET-Universidad Nacional del Comahue, Neuquén, Argentina.
authors.forename: Andrés
authors.initials: A
authors.lastname: Venturino
authors.affiliation: Laboratorio de Efectos Biológicos de Contaminantes Ambientales, Departamento de Bioquímica Humana, Facultad de Medicina, Universidad de Buenos Aires, Argentina.
authors.forename: Noelia
authors.initials: N
authors.lastname: Miret
authors.affiliation: Laboratorio de Efectos Biológicos de Contaminantes Ambientales, Departamento de Bioquímica Humana, Facultad de Medicina, Universidad de Buenos Aires, Argentina.
authors.forename: Andrea
authors.initials: A
authors.lastname: Randi
authors.affiliation: Laboratorio de Radioisótopos, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Argentina.
authors.forename: Elena
authors.initials: E
authors.lastname: Rivera
authors.affiliation: Laboratorio de Radioisótopos, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Argentina.
authors.forename: Mariel
authors.initials: M
authors.lastname: Núñez
authors.affiliation: Laboratorio de Radioisótopos, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Argentina. Electronic address: cmcocca@ffyb.uba.ar.
authors.forename: Claudia
authors.initials: C
authors.lastname: Cocca
mesh_terms: D000975:Antioxidants / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004390:Chlorpyrifos / Q000633:toxicity*; D006801:Humans; D007306:Insecticides / Q000633:toxicity*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D061986:MCF-7 Cells; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D010766:Phosphorylation / Q000187:drug effects
chemical_list: D000975:Antioxidants; D007306:Insecticides; D004390:Chlorpyrifos
keywords: Breast cancer cell lines; Chlorpyrifos; ERK1/2; Hydroxide peroxide; Organophosphorus; Oxidative stress