THE EFFECT OF UNSATURATED FATTY-ACIDS ON MEMBRANE-COMPOSITION AND SIGNAL-TRANSDUCTION IN HT-29 HUMAN COLON-CANCER CELLS

The objective of the present study was to investigate the effect of me mbrane fatty acid (FA) composition on the activity of phospholipase C (PLC) in HT-29 human colon cancer cells. The membrane FA composition w as altered by supplementing cultured cells with FAs of different compo sition. The FAs were stearic acid (18:0; SA), gamma linolenic acid (18 :3 omega 6; gamma LnA); alpha linolenic acid (18:3 omega 3; alpha LnA; ); eicosapentaenoic acid (20:5 omega 3; EPA) and docosahexaenoic acid (22:6 omega 3; DHA). The fatty acids were supplemented as a FA/BSA com plex. Cells supplemented with SA served as the control. Tumor growth w as followed by counting the number of cells in culture. The results in dicate that polyunsaturated fatty acid (PUFA) supplementation had no c onsistent effect on tumor growth from 1 day to another throughout the 15 days of growth. The fatty acid composition of membranes indicates t hat cells incorporated and modified the supplemented fatty acids by de saturation, elongation and retroconversion. The unsaturation index (UI ) of membranes of cells supplemented with EPA and DHA was higher than other groups. PLC activity; measured in the absence of GTP gamma(S) in the assay mixture; was not influenced by membrane FA modification. Ho wever, in the presence of GTP gamma(S) PLC of cells supplemented with 18:3(omega 6) was the lowest among the groups. It has been shown that 18:3(omega 6) accumulated the most in the phosphatidylethanolamine (PE ) fraction. There was a negative correlation between the activity of P LC in the presence of G protein activation and PE 18:3(omega 6) conten t without affecting UI. It was concluded that G protein may be sensiti ve to the level of 18:3(omega 6) content and not to the general fluidi ty of the membranes.