REGULATION OF TUMOR-CELL FATTY-ACID OXIDATION BY N-6 POLYUNSATURATED FATTY-ACIDS

Fatty acids have been shown to regulate the expression of mRNA for bot h lipogenic and glycolytic enzymes in rat liver, The role of fatty aci ds in the regulation of carnitine palmitoyltransferase (CPT) I and II activity in tumour cells was investigated, The polyunsaturated fatty a cids, gamma-linolenic and arachidonic acid, caused 60-70% inhibition o f tumour cell CPT I activity and 45-50% inhibition of [C-14]-palmitic acid oxidation to (CO2)-C-14. These effects were blocked by the cycloo xygenase inhibitor, indomethacin. Prostaglandins E-1 and E-2 caused ma rked inhibition of both CPT I and CPT II activity and inhibition of ce ll proliferation. Prostaglandin E-2 production by tumour cells was inc reased in the presence of arachidonic acid and inhibited when indometh acin was present, The proliferation of the HT29 cell line was unaffect ed as was its CPT I and II activity by both fatty acids and prostaglan dins. CPT I mRNA expression was not inhibited by fatty acids, indeed i t increased in the presence of arachidonic acid and prostaglandin E1. These results strongly suggest that polyunsaturated n-6 fatty acids ar e able, via prostaglandin products, to regulate the CPT activity of ce rtain tumour cells, This may have a considerable impact on mitochondri al beta-oxidation and cellular metabolism of fatty acids, reflected in the marked inhibition of cell proliferation by these fatty acids.