PROSTAGLANDIN SYNTHESIS IN HUMAN CANCER-CELLS - INFLUENCE OF FATTY-ACIDS AND BUTYRATE

Previous research has suggested that prostaglandins (PGs) may play a r ole in the development of colon cancer since tumor cells produce more PGs than normal cells, However, the exact mechanism by which PGs play a role in the development of cancer is not known, In addition, factors that influence PG synthesis are not known since they are complicated by the presence of homeostatic mechanisms, To avoid the homeostatic me chanisms, the present research was designed to examine factors that ma y influence PG synthesis in an in vitro system, i,e, a tissue culture, We have chosen two human colon cancer cell lines that differ in their ability to metabolize long-chain fatty acids (LCFAs), LS174T cells an d HT-29 cells, We examined the effect of LCFAs on their membrane fatty acid composition, growth, and ability to release the main PGs (PGE(2) and PGI). The LCFAs used were those most common in the colonic lumen [18:0, 18:2 (n-6), and 18:3 (n-3)], In addition, we examined the effec t of butyrate on the above mentioned parameters, Butyrate is produced in the colon through fermentation of dietary fibers, The data obtained suggest that although both of these tumor cell lines are of human col onic origin, they differ in their response to LCFAs and butyrate in so me of the characteristics studied, such as growth, composition of memb ranes, and the relationship between membrane FA composition and PG syn thesis, Polyunsaturated fatty acid supplementation stimulated the grow th of HT-29 cells but not of LS174T cells when compared with growth in media supplemented with 18:0, However, the two cell lines were simila r in their response to the stimulatory effect of PG production by buty rate, These butyrate-treated cells produced 40% more PGs compared to t heir controls.