CPF modulates cell migration and invasión in human breast cáncer cells

C VENTURA; C A PONTILLO; A RANDI; A VENTURINO; E RIVERA; C COCCA; M NUÑEZ

Mendoza

Congreso; 48th Annual Meeting Argentine Society for Biochemistry and Molecular Biology.; 2012

Sociedad Argentina de Investigación Bioquímica y Biología Molecular

Chlorpyrifos (CPF) is an organophosphorus pesticide that has been described as an endocrine disruptor. We have demonstrated that environmental doses (50 nM) of CPF induce cell proliferation in estrogen dependent-breast cancer cells. Our objective was to study CPF action on cell migration and invasion in MCF-7 and MDA-MB-231 breast cancer cells. CPF at 0.05, 0.5, 5 and 50 μM were assayed. MMP-2 and MMP-9 gelatinolytic activities were evaluated by gelatin zymography. Wound-healing assay was used to evaluate cell migration. Cell invasion was studied by transwell assays using serum as chemoatractant. Beta-catenin was studied by immunofluorescence microscopy. Our results showed that CPF 0.5 µM induced MDA-MB-231 (66;p lower than 0.05) cell migration accompanied by an augment in gelatinolytic activity (20%;p lower than 0.01). Conversely, CPF 50 µM reduced this activity (50%;p lower than 0.001) in both cell lines. CPF 50 µM increased MCF-7 cell invasion (67%, p lower than 0.05) with an increment in beta-catenin nuclear expression. Cell invasion was inhibited in MDA-MB-231 cells (65%;p lower than 0.001). A selective c-SRC inhibitor, PP2, reversed CPF effects on migration and invasion processes. Our results indicate that CPF at low dose induces MDA-MB-231 cell migration and MMP-2 and MMP-9 may be involved in this effect. Also, the pesticide induces MCF-7 cell invasion which may be related to nuclear beta-catenin expression in this cell line.