Antiangiogenicity of docosahexaenoic acid and its role in the suppression of breast cancer cell growth in nude mice

The addition of the omega-3 fatty acid (n-3 FA) docosahexaenoic acid (DHA), 4%, to a 20% (wt/wt) fat diet containing 4% linoleic acid (LA, n-6 FA) par tially suppressed the growth of the MDA-MB-231 human breast cancer cell lin e as solid tumors in athymic nude mice. This reduced tumor growth was assoc iated with significant inhibition of cell proliferation, as indicated by di minished Ki-67 nuclear proliferation marker expression, and an increase in TUNEL positive (apoptotic) cells (both p<0.001). The microvessel counts wer e also reduced in tumors from the DHA-supplemented dietary group of mice (p <0.001), and this suppression of angiogenesis was positively correlated wit h loss of Ki-67 expression. Tumor vascular endothelial cell growth factor ( VEGF) concentrations were not reduced in the DHA-fed mice. It is postulated that the antiangiogenicity of DHA in this breast cancer model is related t o our demonstrated inhibition of LA-derived prostaglandin E2, 12-hydroxy-ei cosatetraenoic acid (12-HETE) and 15-HETE synthesis, reducing the paracrine stimulation by these known angiogenic eicosanoids on microvessel endotheli al cells.