TY - JOUR T1 - Effects of Phorbol Ester Tumor Promoters on Arachidonic Acid Metabolism in Chick Embryo Fibroblasts JF - Molecular Pharmacology JO - Mol Pharmacol SP - 569 LP - 578 VL - 16 IS - 2 AU - R. A. MUFSON AU - D. DEFEO AU - I. B. WEINSTEIN Y1 - 1979/09/01 UR - http://molpharm.aspetjournals.org/content/16/2/569.abstract N2 - The phorbol ester tumor promoter (12-0-tetradecanoyl-phorbol-13-acetate (10-7-10-9 M) caused a rapid (1-3 hr after addition) release of arachidonic acid and prostaglandins E2 and F2α from chick embryo fibroblasts. This effect was inhibited by cycloheximide and puromycin. Prostaglandin release was more sensitive to inhibition than was arachidonic acid release. Indomethacin, a cyclooxygenase inhibitor, completely blocked TPA-induced prostaglandin synthesis and slightly enhanced arachidonic acid release. Despite the complete suppression of prostaglandin synthesis, indomethacin caused only a 20-30% inhibition of TPA induction of plasminogen activator. Phorbol 12,13-didecanoate, phorbol-l2,13-dibenzoate and mezerein were also potent inducers of arachidonic acid and prostaglandin release, while phorbol and 4α phorbol didecanoate were inactive. All trans retinoic acid (10-5-10-6 M) inhibited TPA-induced arachidonic acid and prostaglandin release; retinyl palmitate and β-carotene were less effective inhibitors. The effects of the phorbol compounds and retinoids on arachidonic acid release in this cell culture system correlate with their known effects on tumor promotion in mouse skin. Deacylation of membrane phospholipids may, therefore, be an important concomitant in the action of this class of tumor promoters. ER -