Aryl hydrocarbon receptor and HIF-1α pathways are involved in the increase in VEGF expression in triple-negative breast cancer cells exposed to the endocrine disruptor chlorpyrifos

BUJÁN S; PONTILLO C; MIRET NV; LEGUIZAMÓN MA; CHIAPPINI F; ZÁRATE L; COCCA C; RANDI A

Congreso; Reunión Anual de Sociedades de Biociencias 2022; 2022

Chlorpyrifos (CPF) is one of the most widely used organophosphate pesticides in agriculture. Breast cancer is the most frequently occurring malignancy in women, and in recent years the exposure to environmental pollutants has gained importance as a risk factor. CPF promotes cell migration and invasion in breast cancer, and binds to the aryl hydrocarbon receptor (AhR), a transcription factor involved in vascular development and tumor progression. Hypoxia Inducible Factor-1α (HIF-1α) induces vital genes in tumor survival, such as Vascular Endothelial Growth Factor (VEGF), Nitric Oxide Synthase-2 (NOS-2) and Cyclooxygenase-2 (COX-2). COX-2 and NOS-2 are pro-inflammatory enzymes that contribute to tumor progression. Our aim was to analyze the CPF action on proangiogenic factors expression like the HIF-1α, VEGF, NOS-2 and COX-2 in triple negative breast cancer cells MDA-MB-231. In addition, we examined whether VEGF secreted by CPF-treated MDA-MB-231 could activate the endothelial cells. Tumor cells were exposed in a dose- (0.05; 0.5; 5 and 50 μM) and time-(6 and 24 h) curves to CPF. Our results showed that CPF (0.05 μM) enhances HIF-1α protein content at 6 and 24 h (p