Hexachlorobenzene stimulates vascular endothelial growth factor secretion in the human breast cancer cell line MCF-7, promoting the angiogenic switch

MARCUCCI, LUCAS; COCCA, CLAUDIA; SALES, MARIA; PONTILLO, CAROLINA; MIRET, NOELIA; ALVAREZ, LAURA; RANDI, ANDREA; ESPAÑOL, ALEJANDRO; CHIAPPINI, FLORENCIA; KLEIMAN DE PISAREV, DIANA

Mérida

Congreso; XIV International Congress of Toxicology; 2016

International Union of Toxicology

Exposure to environmental pollutants may alter proangiogenic ability and promotes tumor growth. Hexachlorobenzene (HCB) is an organochlorine pesticide found in maternal milk and it is a ligand of the aryl hydrocarbon receptor. We have demonstrated that HCB induces proliferation, migration and invasion in human breast cancer cells, as well as tumor growth and metastasis in vivo. Furthermore, we have reported that HCB enhances migration and neovasculogenesis in mammary endothelial cells. Angiogenesis plays a central role in both local tumor growth and distant metastasis. Vascular endothelial growth factor (VEGF), which is secreted by epithelial and endothelial cells, acts on tumor endothelial cells to increase their proliferation, survival, migration and permeability. Cyclooxygenase-2 (COX-2) promotes carcinogenesis, tumor proliferation, angiogenesis and prevention of apoptosis. Nitric oxide synthase 2 (NOS2) is implicated as a component in many aggressive tumor phenotypes, including breast cancer. The aim of our work was to examine the HCB action on breast cancer angiogenesis. We studied the effects of in vivo exposure to HCB (0.3, 3 and 30 mg/kg body weight) for 30 days, in a xenograft model with the human breast cancer cell line estrogen receptor α positive (+ERα) MCF-7 on: a) number of vessels/mm2 (angiogenic switch) and b) VEGF expression in mice skin. Besides, we examined HCB (0.005, 0.05, 0.5 and 5 µM) action in vitro, for 24 hours in MCF-7 on: c) VEGF secretion (Western Blot), d) VEGF expression levels, e) COX-2 and f) NOS2 protein levels (Western Blot). Our results showed that HCB (3 mg/kg body weight) stimulates the angiogenic switch (71%, p