Antiangiogenicity of Docosahexaenoic Acid and Its Role in the Suppression of Breast Cancer Cell Growth in Nude Mice

Int J Oncol. 1999 Nov;15(5):1011-5. doi: 10.3892/ijo.15.5.1011.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Angiogenesis Inhibitors / administration & dosage
  • Angiogenesis Inhibitors / therapeutic use*
  • Animals
  • Apoptosis / drug effects
  • Breast Neoplasms / blood supply
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Dietary Supplements*
  • Docosahexaenoic Acids / administration & dosage
  • Docosahexaenoic Acids / therapeutic use*
  • Fatty Acids, Omega-3 / administration & dosage
  • Fatty Acids, Omega-3 / therapeutic use*
  • Female
  • Humans
  • In Situ Nick-End Labeling
  • Linoleic Acid / administration & dosage
  • Linoleic Acid / therapeutic use
  • Mice
  • Mice, Nude
  • Regression Analysis
  • Safflower Oil / administration & dosage
  • Safflower Oil / therapeutic use
  • Transplantation, Heterologous

Substances

  • Angiogenesis Inhibitors
  • Fatty Acids, Omega-3
  • Docosahexaenoic Acids
  • Safflower Oil
  • Linoleic Acid