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

CAROLINA PONTILLO; NOELIA MIRET; ALEJANDRO ESPAÑOL; LORENA ZÁRATE; FLORENCIA CHIAPPINI; MARÍA ELENA SALES; DIANA KLEIMAN; CLAUDIA COCCA; ANDREA RANDI

Buenos Aires

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

Edith Kordon, Claudia Lanari

Angiogenesis plays a role in local tumor growth and metastasis. Elevated levels of HypoxiaInducible Factor-1α (HIF-1α) correlate with angiogenesis. HIF-1α induces gene expression likeCyclooxygenase-2 (COX-2), Nitric Oxide Synthase-2 (NOS-2) and Vascular Endothelial GrowthFactor (VEGF). COX-2 and NOS-2 promote tumor angiogenesis. VEGF increases endothelial cellsproliferation, survival and migration. Endocrine disruptors Hexachlorobenzene (HCB) andChlorpyrifos (CPF) induce cell proliferation and tumor growth in breast cancer animal models. Ouraim was to examine their action on breast cancer angiogenesis. We studied HCB (0.005, 0.05, 0.5and 5 μM) or CPF (0.05, 0.5, 5 and 50 μM) effect in MDA-MB 231 triple negative breast cancer cellson: HIF-1α, COX-2 and NOS-2 protein levels, VEGF expression and secretion (Western Blot). Ourresults showed that exposure to 6 h of HCB enhances HIF-1α levels at 0.05, 0.5 and 5 μM, andNOS-2 expression and VEGF secretion at all assayed doses. In addition, at 24 h HCB (0.05 and 5μM) increases COX-2 levels (p<0.05). Moreover, CPF for 6 h enhances HIF-1α and NOS-2expression at all assayed doses, as well as VEGF secretion at 0.05, 0.5 and 5 μM. Besides, CPF(0.05, 0.5 and 5 μM) stimulates COX-2 levels at 24 h (p<0.05). We demonstrated that HCB and CPFinduce the proangiogenic factors expression. In conclusion, these data highlight that the exposureto endocrine disruptors could contribute to mammary carcinogenesis, promoting angiogenesis.