Chlorpyrifos inhibits cell proliferation through ERK1/2 phosphorylation in breast cancer cell lines. (February 2015)

• Record Type: Journal Article
• Authors: Ventura, Clara; Venturino, Andrés; Miret, Noelia; Randi, Andrea; Rivera, Elena; Núñez, Mariel; Cocca, Claudia
• Is Part Of: Chemosphere. Volume 120(2015)
• Page Start: 343
• Page End: 350
• Publication Date: 2015-02
• Subjects: CPF chlorpyrifos -- OP organophosphate insecticides -- ROS reactive oxygen species -- RNS reactive nitrogen species -- SOD superoxide dismutase -- CAT catalase -- GSH reduced glutathione -- GPX glutathione peroxidase -- TBARS 2-thiobarbituric acid reactant substances -- MDA malondialdehide -- PUFAs polyunsaturated fatty acids; Organophosphorus -- Chlorpyrifos -- Breast cancer cell lines -- ERK1/2 -- Oxidative stress -- Hydroxide peroxide; Pollution -- Periodicals; Pollution -- Physiological effect -- Periodicals; Environmental sciences -- Periodicals; Atmospheric chemistry -- Periodicals; 551.511
• DOI: 10.1016/j.chemosphere.2014.07.088
• Languages: English
• ISSNs: 0045-6535

Abstract

Highlights: Chlorpyrifos (CPF) insecticide is used to control pest worldwide. CPF 50 μM inhibited breast cancer cell proliferation by redox imbalance. H2 O2 is the main specie involved in cell proliferation inhibition by CPF. H2 O2 produced by CPF promotes the phosphorylation of ERK1/2 leading to cell death. 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 H2 O2 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.