Angiogenic potential of an organochlorine pesticide in breast cancer. In vitro and in vivo studies

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

Mar del Plata

Congreso; LXI Reunión Científica Anual de la Sociedad Argentina de Investigación Clínica; 2016

Sociedad Argentina de Investigación Clínica

Epidemiological studies report that exposure to organochlorine pesticides like hexachlorobenzene (HCB) increases risk of cancer. We demonstrated that HCB induces proliferation, migration, and invasion in human breast cancer cells as well as enhances neovasculogenesis in mammary endothelial cells. Vascular endothelial growth factor (VEGF) and cyclooxygenase-2 (COX-2) promotes carcinogenesis, tumor proliferation and angiogenesis. Nitric oxide (NO) is implicated in cancer biology and tumor progression. Inducible nitric oxide synthase (NOS2) is an important mediator of tumor aggressiveness, however, it should be noted that other isoforms, NOS1 and NOS3, are also implicated. This study examined the HCB action on breast cancer angiogenesis using a xenograft model in mice exposed to HCB (0.3, 3 and 30 mg/kg body weight, b.w.), with the human breast cancer cell line MCF-7 (+ERα), and, MCF-7 cells treated with HCB (0.005, 0.05, 0.5 and 5 µM). Results: HCB (3 mg/kg b.w.) stimulated the angiogenic switch evaluated as the number of vessels/mm2 (71% p