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Regulation of tumour cell fatty acid oxidation by n‐6 polyunsaturated fatty acids
Author(s) -
Colquhoun Alison,
de Mello Fábio E. P.,
Curi Rui
Publication year - 1998
Publication title -
iubmb life
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.132
H-Index - 113
eISSN - 1521-6551
pISSN - 1521-6543
DOI - 10.1080/15216549800201152
Subject(s) - arachidonic acid , polyunsaturated fatty acid , biochemistry , fatty acid , prostaglandin , carnitine , metabolism , cyclooxygenase , chemistry , cell growth , carnitine palmitoyltransferase i , fatty acid metabolism , biology , eicosanoid , beta oxidation , enzyme
Fatty acids have been shown to regulate the expression of mRNA for both lipogenic and glycolytic enzymes in rat liver. The role of fatty acids in the regulation of carnitine palmitoyltransferase (CPT) I and II activity in tumour cells was investigated. The polyunsaturated fatty acids, γ‐linolenic and arachidonic acid, caused 60‐70% inhibition of tumour cell CPT I activity and 45‐50% inhibition of [ 14 C]‐palmitic acid oxidation to 14CO2. These effects were blocked by the cyclooxygenase inhibitor, indomethacin. Prostaglandins E1 and E2 caused marked inhibition of both CPT I and CPT II activity and inhibition of cell proliferation. Prostaglandin E2 production by tumour cells was increased in the presence of arachidonic acid and inhibited when indomethacin was present. The proliferation of the HT29 cell line was unaffected as was its CPT I and II activity by both fatty acids and prostaglandins. CPT I mRNA expression was not inhibited by fatty acids, indeed it increased in the presence of arachidonic acid and prostaglandin E1. These results strongly suggest that polyunsaturated n‐6 fatty acids are able, via prostaglandin products, to regulate the CPT activity of certain tumour cells. This may have a considerable impact on mitochondrial β‐oxidation and cellular metabolism of fatty acids, reflected in the marked inhibition of cell proliferation by these fatty acids.