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

Abstract

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.

• Authors: A Vecchini, V Ceccarelli, F Susta, P Caligiana, P Orvietani, L Binaglia, G Nocentini, C Riccardi, G Calviello, P Palozza, N Maggiano, P Di Nardo
• Journal: Journal of lipid research (J Lipid Res) Vol. 45 Issue 2 Pg. 308-16 (Feb 2004) ISSN: 0022-2275 [Print] United States
• PMID: 14563831 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 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

Topics

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