Pesticides exposure enhances HIF-1α, VEGF and NOS-2 expression in MDA-MB-231 human breast cancer cells

PONTILLO, C.; MIRET, N.; ESPAÑOL A; ZARATE, L; CHIAPPINI, F; SALES, ME; KLEIMAN DE PISAREV, D; COCCA, C; RANDI, A

Congreso; LXIV Reunión Científica Anual de la Sociedad Argentina de Investigación Clínica (SAIC); 2019

Organochlorine pesticides such as Hexachlorobenzene (HCB) and organophosphate Chlorpyrifos (CPF) are synthetic compounds used worldwide as insecticides, herbicides and fungicides. Recently, HCB and CPF have become important as a potential risk factor in breast cancer. We demonstrated that these compounds induce proliferation, migration and invasion in human breast cancer cells. Angiogenesis plays a role in local tumor growth and metastasis. It has been observed a correlation between elevated levels of hypoxia inducible factor-1 alpha (HIF-1alpha), tumor metastasis and angiogenesis. HIF-1alpha induces 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 tumor angiogenesis. The aim of our work was to examine the HCB or CPF action on breast cancer angiogenesis. We studied the effects of HCB (0.005, 0.05, 0.5 and 5 μM) or CPF (0.05, 0.5, 5 and 50 μM) exposure in MDA-MB-231 breast cancer cells in dose-response curves on: a) HIF-1alpha expression, b) VEGF secretion, c) COX-2 and d) NOS-2 protein levels (Western blot). Our results showed that MDA-MB-231 exposed for 6 h to CPF increases HIF-1alpha (p