18 1 N7 FATTY-ACIDS INHIBIT GROWTH AND DECREASE INOSITOL PHOSPHATE RELEASE IN HT-29 CELLS COMPARED TO N9 FATTY-ACIDS/

Studies have shown that trans fatty acids may play a role in the devel opment of chronic diseases such as heart disease and cancer. The objec tive of the present project was to examine the effect of supplementati on with 18:1 isomers, both positional and geometrical, as compared to 18:0 on the growth, membrane fatty acid composition and the phosphoino sitide cycle of HT-29 human colon cancer cells. Cells were supplemente d with 30 mu M stearic acid (18:0), elaidic acid (18:1, n9, trans), ol eic acid (18:1, n9, cis), vaccenic acid (18:1, n7, cis) or trans-vacce nic acid (18:1, n7, trans) as sodium salts complexed to fatty acid-fre e bovine serum. Cells were grown in these media for 9 days. Cell growt h was examined by counting the number of cells and expressed as percen tage of control (18:0 supplemented cells). The phosphoinositide (PI) c ycle was examined by measuring the inositol phosphate (IF) released fr om phosphoinositides in the absence (basal) or presence of stimuli (0. 1 mM carbachol, 0.1 mM A(23187) or 20 mM NaF). The results obtained in dicated that cis and trans n7 fatty acids inhibited the growth of HT-2 9 cells by 11% and 23%, respectively, as compared to 18:0 supplementat ion. 18:1, n9 had no effect on tumor growth. Supplementation with all forms of 18:1 resulted in an increase in IP and IP2 production as comp ared to 18:0 supplemented cells without influencing IP3. The presence of the double bond at the 9 position in the supplemented fatty acid in creases total IP production by 59% and in the cis form by 37% above th e control. The breakdown of phosphoinositides in the absence and prese nce of several stimuli supports the observed finding on IP. Trans fatt y acid supplementation resulted in lower hydrolysis of PI as compared to cis fatty acids. It is concluded that the observed inhibition of tu mor growth by the vaccenic acids may be mediated by their effect(s) on the PI cycle which may be associated with their incorporation into me mbrane lipids.