PESTICIDES EXPOSURE ENHANCE HIF-1ALPHA, VEGF AND NOS-2 EXPRESSION IN MDA-MB-231 HUMAN BREAST CANCER CELLS

ESPAÑOL, ALEJANDRO; SALES, MARIA ELENA; RANDI, ANDREA; MIRET, NOELIA; CHIAPPINI, FLORENCIA; COCCA, CLAUDIA; PONTILLO, CAROLINA; ZÁRATE, LORENA; KLEIMAN DE PISAREV, DIANA

Mar del Plata

Congreso; Reunión Anual de Sociedades de Biociencias 2019; 2019

SAIC-SAFE-SAB-SAP

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