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

PONTILLO CAROLINA; MIRET NOELIA; ESPAÑOL ALEJANDRO; ZARATE LORENA; CHIAPPINI FLORENCIA; SALES ME; KLEIMAN DE PISAREV D; COCCA CLAUDIA; RANDI ANDREA

Congreso; Reunión anual de Sociedades Biocientíficas 2019 LXIV Reunión Anual de la 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-1α (HIF-1α), tumor metastasis and angiogenesis. HIF-1α 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-1α 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-1α (p