El pesticida clorpirifos induce fosforilación de Gsk-3β y translocación nuclear de β-catenina en células de adenicarcinoma mamario humano. Consecuencias sobre la capacidad invasiva celular.

VENTURA C, PONTILLO C, MIRET N, RANDI A, VENTURINO A, RIVERA E, COCCA C, NUÑEZ M

Jornada; XXIX Jornadas Multidisciplinarias de Oncología del Instituto “Ángel H. Roffo”; 2013

Instituto “Ángel H. Roffo”

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. β-catenin was studied by immunofluorescence microscopy. Our results showed that CPF 0.5 µM induced MDA-MB-231 (66;p<0.05) cell migration accompanied by an augment in gelatinolytic activity (20%;p<0.01).  Conversely, CPF 50 µM reduced this activity (50%;p<0.001) in both cell lines. CPF 50 µM increased MCF-7 cell invasion (67%, p<0.05) with an increment in β-catenin nuclear expression. Cell invasion was inhibited in MDA-MB-231 cells (65%;p<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-231cell 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 β-catenin expression in this cell line.