New insights on pesticide exposure as a risk factor in breast cancer

PONTILLO C; MIRET N; ESPAÑOL A; ZÁRATE L; CHIAPPINI F; SALES ME; COCCA C; RANDI A

Mar del Plata

Congreso; LXIII Reunión Científica Anual de la Sociedad Argentina de Investigación Clínica; 2018

The incidence of breast cancer is increasing and exposure to pesticides like hexachlorobenzene (HCB) and chlorpyrifos (CPF) has become important as a potential risk factor. These compounds may alter proangiogenic ability and promotes tumor growth. Regional studies show the presence of HCB and CPF in human serum and breast milk. We demonstrated that these compounds induce proliferation, migration and invasion in human breast cancer cells. Angiogenesis plays a role in both local tumor growth and distant metastasis. There is a correlation between elevated levels of Hypoxia Inducible Factor-1α (HIF-1α), tumor metastasis and angiogenesis. HIF-1α induces target genes like Vascular Endothelial Growth Factor (VEGF), Nitric Oxide Synthase-2 (NOS-2) and Cyclooxygenase-2 (COX-2). VEGF acts on tumor endothelial cells to increase their proliferation, survival and migration. COX-2 and NOS-2 promote carcinogenesis and angiogenesis. The aim of our work was to examine the HCB or CPF action on breast cancer angiogenesis. We studied the effects of in vitro exposure to HCB (0.05 and 5 µM) or CPF (0.05 µM), for 6 and 24 hours in MDA-MB-231 breast cancer cells on: a) HIF-1α expression, b) VEGF secretion, c) VEGF expression levels, d) COX-2 and e) NOS2 protein levels (Western Blot). Our results showed that MDA-MB-231 exposed for 6 hours to CPF (0.05 µM), increases HIF-1α (p