Exposure to endocrine disruptors induces proangiogenic factors in MDA-MB-231 human breast cancer cells

PONTILLO C P; ZÁRATE LV (1), PONTILLO CA (1), ESPAÑOL A (2), MIRET NV (1), CHIAPPINI F (1), COCCA C (3), ÁLVAREZ L (1), KLEIMAN DE PISAREV DL (1), SALES ME (2), RANDI AS (1); ESPAÑOL A; ZÁRATE L; CHIAPPINI F; SALES ME; KLEIMAN DE PISAREV; COCCA C3; RANDI A

Congreso; Buenos Aires Breast Cancer Symposium BA-BCS 2020; 2021

Angiogenesis plays a role in local tumor growth and metastasis. Elevated levels of Hypoxia Inducible Factor-1α (HIF-1α) correlate with angiogenesis. HIF-1α induces gene expression like Cyclooxygenase-2 (COX-2), Nitric Oxide Synthase-2 (NOS-2) and Vascular Endothelial Growth Factor (VEGF). COX-2 and NOS-2 promote tumor angiogenesis. VEGF increases endothelial cells proliferation, survival and migration. Endocrine disruptors Hexachlorobenzene (HCB) and Chlorpyrifos (CPF) induce cell proliferation and tumor growth in breast cancer animal models. Our aim was to examine their action on breast cancer angiogenesis. We studied HCB (0.005, 0.05, 0.5 and 5 μM) or CPF (0.05, 0.5, 5 and 50 μM) effect in MDA-MB 231 triple negative breast cancer cells on: HIF-1α, COX-2 and NOS-2 protein levels, VEGF expression and secretion (Western Blot). Our results showed that exposure to 6 h of HCB enhances HIF-1α levels at 0.05, 0.5 and 5 μM, and NOS-2 expression and VEGF secretion at all assayed doses. In addition, at 24 h HCB (0.05 and 5 μM) increases COX-2 levels (p