CHLORPYRIFOS PROMOTES THE MIGRATION OF BREAST CANCER CELLS ACTIVATING C-SRC, AKT, GSK-3 beta AND p38 PATHWAYS

MARIANELA LASAGNA; CLARA VENTURA; SOLEDAD HIELPOS; MARIANA MADIROSIAN; NOELIA MIRET; ANDREA RANDI; MARIEL NÚÑEZ; CLAUDIA COCCA

Virtual

Congreso; Reunión Anual de Sociedades de Biociencias; 2020

Sociedad Argentina de Investigación Clínica, Sociedad Argentina de Fisiología y Sociedad Argentina de Inmunología

Chlorpyrifos (CPF) is a pesticide whose effects on breast cancer riskare not clear. Our aim was to analyze if CPF promotes migration and thepathways involved in MCF-7 and MDA-MB-231 cell lines. Migration was evaluatedby 2D (wound healing and Boyden Chamber assays) and 3D assays (multicellularspheroids). c-Src, AKT, P38 and GSK3-βwere studied by Western Blot. In MCF-7cells, 0.05 μM CPF induced the migration after 48 h(p<0.01) that was reversed withIC182,780 (1 nM) and PP2 (1 μM) together (p<0.001). 50 μM CPF (p<0.001) promoted the migration in ac-Src-dependent way (p<0.001). 0.05 (p<0.001) and 50 μM (p<0.01) CPF induced migration migration on3D model after 5 days. This increment induced by 0.05 μM and 50 μMCPF was retarded in presence ofIC182,780 (p<0.01 and p<0.05,respectively). No changes were observed after adding PP2. Migration induced by0.05 μM and 50 μMwas retarded by adding IC182,780 and PP2 (p< 0.001). Healing assays showedthat migration induced by 0.05 μMCPF (p < 0.001) and 50 μM CPF (p< 0.001) wasreverted by addingPP2 (p< 0.001) after 24 h in MDA-MB-231 cells.c-Src-dependent-migration was also promoted by 0.05 μM and 50 μMCPF (p< 0.05) in Boyden chamber assays. In MCF-7 cells 2D culture, 0.05(p<0.01) and 50 μM CPF (p<0.001) increasedp-c-Src after15 min. p-AKT was induced by 0.05 μMCPF after 60 min in ERα-dependent way (p<0.05).p-AKT was also induced by 50 μM CPF depending on c-Src(p<0.05). p-GSK-3β was induced by 0.05 μM CPF after 60 min in ERα (p<0.01) and c-Src (p<0.01) dependentway. p-P38 induced by 0.05 (p<0.01) and 50 μMCPF (p<0.05) was dependent on c-Src. In MDA-MB-231 cells, CPF inducedp-c-Src after 30 min (p< 0.05) and 60 min(p<0.001). p-AKT was increasedby CPF in an independent way of c-Src activation. p-P38 and p-GSK-3β could be countered by PP2. We show that CPFpromotes the migration of breast cancer cells activating c-Src, AKT, GSK-3β and P38 pathways pointing out importance tominimize the exposure to the pesticide.&amp;amp;lt;!-- /* Font Definitions */ @font-face{font-family:"Cambria Math";panose-1:2 4 5 3 5 4 6 3 2 4;mso-font-charset:0;mso-generic-font-family:roman;mso-font-pitch:variable;mso-font-signature:3 0 0 0 1 0;}@font-face{font-family:Calibri;panose-1:2 15 5 2 2 2 4 3 2 4;mso-font-charset:0;mso-generic-font-family:swiss;mso-font-pitch:variable;mso-font-signature:-536859905 -1073732485 9 0 511 0;} /* Style Definitions */ p.MsoNormal, li.MsoNormal, div.MsoNormal{mso-style-unhide:no;mso-style-qformat:yes;mso-style-parent:"";margin:0cm;mso-pagination:widow-orphan;font-size:12.0pt;font-family:"Calibri",sans-serif;mso-ascii-font-family:Calibri;mso-ascii-theme-font:minor-latin;mso-fareast-font-family:Calibri;mso-fareast-theme-font:minor-latin;mso-hansi-font-family:Calibri;mso-hansi-theme-font:minor-latin;mso-bidi-font-family:"Times New Roman";mso-bidi-theme-font:minor-bidi;mso-ansi-language:ES-TRAD;mso-fareast-language:EN-US;}.MsoChpDefault{mso-style-type:export-only;mso-default-props:yes;font-family:"Calibri",sans-serif;mso-ascii-font-family:Calibri;mso-ascii-theme-font:minor-latin;mso-fareast-font-family:Calibri;mso-fareast-theme-font:minor-latin;mso-hansi-font-family:Calibri;mso-hansi-theme-font:minor-latin;mso-bidi-font-family:"Times New Roman";mso-bidi-theme-font:minor-bidi;mso-fareast-language:EN-US;}size:612.0pt 792.0pt;margin:70.85pt 3.0cm 70.85pt 3.0cm;mso-header-margin:36.0pt;mso-footer-margin:36.0pt;mso-paper-source:0;}div.WordSection1{page:WordSection1;}