Breast Cancer Cells Exposed to Pesticides Enhance Vascular Endothelial Growth Factor Secretion and Activate Endothelial Cells Promoting Angiogenesis

BUJÁN S; CAROLINA PONTILLO, , , , , , Y; MIRET, NOELIA; LEGUIZAMÓN M. AGUSTINA; CHIAPPINI F; ZARATE LORENA; COCCA C; RANDI A

Congreso; Society of Environmental Toxicology and Chemistry (SETAC) Latin America 15th Biennial Meeting; 2023

Chlorpyrifos (CPF) is one of the most widely used organophosphate pesticides in agriculture.Hexachlorobenzene (HCB) was used as a fungicide in the past and is still released into the environment as a byproduct from industrial processes. CPF and HCB bind weakly to the Aryl Hydrocarbon Receptor (AhR), a transcription factor involved in vascular development and tumor progression. Breast cancer is the most frequently occurring malignancy in women, and in recent years the exposure to pesticides has gained importance as a risk factor acting like endocrine disruptors. CPF and HCB promote cell migration and invasion in breast cancer cells, as well as mammary tumor growth. 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). Our objective was to evaluate the CPF and HCB action on proangiogenic factors expression like HIF-1α, VEGF, NOS-2 and COX-2 in triple negative breast cancer cells MDA-MB-231. In addition, we examined whether conditioned medium (CM) of pesticides treated MDA-MB-231 could activate the endothelial cells. Tumor cells were treated with CPF (0.05; 0.5; 5 and 50 μM) or HCB (0.005; 0.05; 0.5 and 5 μM) at 1, 6 and 24 h. Endothelial cells were exposed to CM from tumor cells treated with pesticides (0.05 μM) for 6 h, and cell proliferation and migration were assayed.Results in MDA-MB-231 cells showed that CPF and HCB (0.05 μM) enhance HIF-1α protein content (28%, p