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) partially suppressed the growth of the MDA-MB-231 human breast cancer cell line as solid tumors in athymic nude mice. This reduced tumor growth was associated with significant inhibition of cell proliferation, as indicated by diminished Ki-67 nuclear proliferation marker expression, and an increase in TUNEL positive (apoptotic) cells (both p<0.001). The microvessel counts were also reduced in tumors from the DHA-supplemented dietary group of mice (p<0.001), and this suppression of angiogenesis was positively correlated with 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 to our demonstrated inhibition of LA-derived prostaglandin E2, 12-hydroxyeicosatetraenoic acid (12-HETE) and 15-HETE synthesis, reducing the paracrine stimulation by these known angiogenic eicosanoids on microvessel endothelial cells.
Rose
D P
DP
Division of Nutrition and Endocrinology, American Health Foundation, Valhalla, NY 10595, USA.
Connolly
J M
JM
D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D019587:Dietary Supplements; D004281:Docosahexaenoic Acids / Q000008:administration & dosage / Q000627:therapeutic use*; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D020287:In Situ Nick-End Labeling; D019787:Linoleic Acid / Q000008:administration & dosage / Q000627:therapeutic use; D051379:Mice; D008819:Mice, Nude; D012044:Regression Analysis; D012450:Safflower Oil / Q000008:administration & dosage / Q000627:therapeutic use; D014183:Transplantation, Heterologous
D020533:Angiogenesis Inhibitors; D015525:Fatty Acids, Omega-3; D004281:Docosahexaenoic Acids; D012450:Safflower Oil; D019787:Linoleic Acid