Dietary alpha-linolenic acid reduces COX-2 expression and induces apoptosis of hepatoma cells

J Lipid Res. 2004 Feb;45(2):308-16. doi: 10.1194/jlr.M300396-JLR200. Epub 2003 Oct 16.


Fatty acid synthetase (FAS) is overexpressed in various tumor tissues, and its inhibition and/or malonyl-CoA accumulation have been correlated to apoptosis of tumor cells. It is widely recognized that both omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) depress FAS expression in liver, although epidemiological and experimental reports attribute antitumor properties only to omega-3 PUFA. Therefore, we investigated whether lipogenic gene expression in tumor cells is differently regulated by omega-6 and omega-3 PUFAs. Morris hepatoma 3924A cells were implanted subcutaneously in the hind legs of ACI/T rats preconditioned with high-lipid diets enriched with linoleic acid or alpha-linolenic acid. Both-high lipid diets depressed the expression of FAS and acetyl-CoA carboxylase in tumor tissue, this effect correlating with a decrease in the mRNA level of their common sterol regulatory element binding protein-1 transcription factor. Hepatoma cells grown in rats on either diet did not accumulate malonyl-CoA. Apoptosis of hepatoma cells was induced by the alpha-linolenic acid-enriched diet but not by the linoleic acid-enriched diet. Therefore, in this experimental model, apoptosis is apparently independent of the inhibition of fatty acid synthesis and of malonyl-CoA cytotoxicity. Conversely, it was observed that apoptosis induced by the alpha-linolenic acid-enriched diet correlated with a decrease in arachidonate content in hepatoma cells and decreased cyclooxygenase-2 expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetyl-CoA Carboxylase / genetics
  • Acetyl-CoA Carboxylase / metabolism
  • Animals
  • Apoptosis / drug effects*
  • Apoptosis / genetics
  • CCAAT-Enhancer-Binding Proteins / genetics
  • Cyclooxygenase 2
  • Diet
  • Dietary Fats, Unsaturated
  • Down-Regulation / genetics
  • Fatty Acid Synthases / genetics
  • Fatty Acid Synthases / metabolism
  • Fatty Acids, Omega-6 / genetics
  • Fatty Acids, Omega-6 / metabolism
  • Fatty Acids, Unsaturated / genetics
  • Fatty Acids, Unsaturated / metabolism
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Isoenzymes / biosynthesis
  • Isoenzymes / genetics*
  • Liver Neoplasms, Experimental / drug therapy
  • Liver Neoplasms, Experimental / genetics
  • Liver Neoplasms, Experimental / metabolism
  • Liver Neoplasms, Experimental / pathology*
  • Prostaglandin-Endoperoxide Synthases / biosynthesis
  • Prostaglandin-Endoperoxide Synthases / genetics*
  • Rats
  • alpha-Linolenic Acid / administration & dosage*
  • alpha-Linolenic Acid / metabolism


  • CCAAT-Enhancer-Binding Proteins
  • Dietary Fats, Unsaturated
  • Fatty Acids, Omega-6
  • Fatty Acids, Unsaturated
  • Isoenzymes
  • alpha-Linolenic Acid
  • Cyclooxygenase 2
  • Prostaglandin-Endoperoxide Synthases
  • Fatty Acid Synthases
  • Acetyl-CoA Carboxylase