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 promotion in mice. Because little is known about the deposition of CLA into 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 keratinocytes. When keratinocytes (HEL-30) were grown in media containing 14C-CLA for various periods, more than 50% of the 14C-CLA was incorporated into cellular lipids by 9 h. The distribution of CLA in phospholipid classes was similar to LA, Approximately 50% of 14C-LA and 14C-CLA were incorporated into phosphatidylcholine (PC), while the remainder was taken up by phosphatidylethanolamine (PE) and phosphatidylserine/phosphatidylinositol (PS/PI). In contrast, 14C-AA was more equitably distributed into PC, PE, or PS/PI (27, 30, or 38%, respectively). When keratinocytes were prelabeled with radiolabeled fatty acids, phorbol ester-induced release of 14C-CLA was 1.5 times higher than 14C-LA and 14C-AA. However, 14C-prostaglandin E (PGE) release in 14C-CLA prelabeled cultures was 6 and 13 times lower than cultures treated with 14C-LA and 14C-AA, respectively. Moreover, the ability of non-radiolabeled CLA to support ornithine decarboxylase activity, a hallmark event of tumor promotion, was significantly lower than in LA- and AA-treated cultures. These studies suggest that CLA inhibits skin tumor promotion, in part, through a PGE-dependent mechanism.
Liu
K L
KL
Department of Foods and Nutrition, Purdue University, West Lafayette, Indiana 47906, USA.
Belury
M A
MA
D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism; D002273:Carcinogens / Q000378:metabolism / Q000494:pharmacology*; D002460:Cell Line; D004347:Drug Interactions; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism; D008041:Linoleic Acids / Q000378:metabolism / Q000494:pharmacology*; D051379:Mice; D009369:Neoplasms / Q000209:etiology; D009955:Ornithine Decarboxylase / Q000187:drug effects; D010743:Phospholipids / Q000737:chemistry; D011458:Prostaglandins E / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000378:metabolism / Q000494:pharmacology*
D001095:Arachidonic Acids; D002273:Carcinogens; D008041:Linoleic Acids; D010743:Phospholipids; D011458:Prostaglandins E; D009955:Ornithine Decarboxylase; D013755:Tetradecanoylphorbol Acetate