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

Gabriella Calviello, Paola Palozza, Nicola Maggiano

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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.
Lingua originaleEnglish
pagine (da-a)308-316
Numero di pagine9
RivistaJournal of Lipid Research
Stato di pubblicazionePubblicato - 2004


  • COX-2
  • alpha-linolenic acid
  • apoptosis
  • hepatoma


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