CONJUGATED LINOLEIC-ACID MODULATION OF PHORBOL ESTER-INDUCED EVENTS IN MURINE KERATINOCYTES

Recent work in our lab has shown that the chemoprotective fatty acid, conjugated linoleic acid (CLA), inhibits phorbol ester skin tumor prom otion in mice. Because little is known about the deposition of CLA int o tissues as well as its biological activity, this study compared the incorporation and biological activity of CLA to linoleic acid (LA; 18: 2, c9,c12) and arachidonic acid (AA; 20:4 c5,c8,c11,c14) in cultured k eratinocytes. When keratinocytes (HEL-30) were grown in media containi ng C-14-CLA for various periods, more than 50% of the C-14-CLA was inc orporated into cellular lipids by 9 h. The distribution of CLA in phos pholipid classes was similar to LA. Approximately 50% of C-14-LA and C -14-CLA were incorporated into phosphatidylcholine (PC), while the rem ainder was taken up by phosphatidylethanolamine (PE) and phosphatidyl- serine/phosphatidylinositol (PS/PI). In contrast, C-14-AA was more equ itably distributed into PC, PE, or PS/PI (27, 30, or 38%, respectively ). When keratinocytes were prelabeled with radio-labeled fatty acids, phorbol ester-induced release of C-14-CLA was 1.5 times higher than C- 14-LA and C-14-AA. However, C-14-prostaglandin E (PGE) release in C-14 -CLA prelabeled cultures was 6 and 13 times lower than cultures treate d with C-14-LA and C-14-AA, respectively. Moreover, the ability of non -radiolabeled CLA to support ornithine decarboxylase activity, a hallm ark event of tumor promotion, was significantly lower than in LA- and AA-treated cultures. These studies suggest that CLA inhibits skin tumo r promotion, in part, through a PGE-dependent mechanism.