Effects of Reduced Dietary Linoleic Acid Intake, Alone or Combined With an Algal Source of Docosahexaenoic Acid, on MDA-MB-231 Breast Cancer Cell Growth and Apoptosis in Nude Mice

Nutr Cancer. 1999;35(1):44-9. doi: 10.1207/S1532791444-49.

Abstract

Diets rich in linoleic acid (LA), an n-6 fatty acid, stimulate the progression of human breast cancer cell solid tumors in athymic nude mice, whereas docosahexaenoic acid (DHA) and eicosapentaenoic acid, long-chain n-3 fatty acids, exert suppressive effects. In the present study we used a novel source of DHA, in triglyceride form, to determine the effects of feeding low levels of the fatty acid on the growth of MDA-MB-231 cells injected into the thoracic mammary fat pads of female nude mice. Four different isocaloric diets were used, all of which provided 20% (wt/wt) total fat. The control diets contained 8% (20 mice) or 4% (50 mice) LA; the n-3 fatty acid-supplemented groups of 50 mice were fed 4% LA-containing diets plus 2% or 4% DHA. The tumor growth rates were reduced significantly in mice fed the 4% LA compared with the 8% LA diet; the addition of 4% DHA to the 4% LA-containing diet produced a further reduction in tumor growth rate (p < or = 0.003 at and after Week 6). The final tumor weights were also reduced in the DHA-fed mice compared with the 8% LA dietary group (2% DHA, p = 0.02; 4% DHA, p = 0.01) and in the 4% DHA-fed mice compared with the 4% LA control group (p = 0.02); a similar trend for mice fed the lower level of DHA did not achieve statistical significance. Tumor prostaglandin E2 concentrations were reduced by feeding the lower LA level; further dose-dependent decreases occurred in the DHA dietary groups and were accompanied by reduced levels of 12- and 15-hydroxyeicosatetraenoic acids. These changes in eicosanoid biosynthesis may have been responsible for the observed decreases in cell proliferation, indicated by suppressed Ki-67 expression, and increases in apoptotic activity, as reflected in TdT-mediated dUTP nick end labeling immunohistochemical staining.

Publication types

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

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Body Weight / drug effects
  • Cell Division / drug effects
  • Dietary Fats, Unsaturated / administration & dosage
  • Dietary Fats, Unsaturated / pharmacology*
  • Docosahexaenoic Acids / administration & dosage
  • Docosahexaenoic Acids / pharmacology*
  • Dose-Response Relationship, Drug
  • Eicosanoids / analysis
  • Female
  • Humans
  • Immunohistochemistry
  • In Situ Nick-End Labeling
  • Ki-67 Antigen / analysis
  • Linoleic Acid / deficiency*
  • Mammary Neoplasms, Experimental / etiology
  • Mammary Neoplasms, Experimental / pathology*
  • Mice
  • Mice, Nude
  • Tumor Cells, Cultured

Substances

  • Dietary Fats, Unsaturated
  • Eicosanoids
  • Ki-67 Antigen
  • Docosahexaenoic Acids
  • Linoleic Acid