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Papers In Press, published online ahead of print October 16, 2003
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Internal Medicine, University of Perugia, Perugia 06126
Corresponding Author: binaglia{at}unipg.it
Fatty acid synthetase 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 PUFA depress fatty acid synthetase expression in liver although epidemiological and experimental reports attribute antitumor properties only to omega-3 PUFA. Therefore, we investigated to evaluate whether lipogenic gene expression in tumor cells is differently regulated by omega-6 and omega-3 PUFA. Morris hepatoma 3924A cells were implanted subcutaneously in the hind legs of ACI/T rats pre-conditioned with high lipid diets enriched with linoleic acid or alpha-linolenic acid. Both high lipid diets depressed the expression of fatty acid synthetase and acetyl-CoA carboxylase in tumor tissue, this effect correlating with a decrease in the mRNA level of their common SREBP-1 transcription factor. Hepatoma cells grown in rats on either diets 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 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 a decreased cyclooxygenase-2 expression
Revised on October 14, 2003
Accepted on October 14, 2003
Dietary
-linolenic acid reduces COX-2 expression and induces apoptosis of hepatoma cells
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