Differential effects of free and liposome-associated 1-O-octadecyl-2-O-methylglycerophosphocholine on protein kinase C

Incorporation of ET-18-OCH3 into well-characterized liposomes known as ELL- 12 has eliminated its gastrointestinal and hemolytic toxicity without loss of growth inhibiting activity. ET-18-OCH3, but not ELL-12, blunted the incr ease in membrane protein kinase C (PKC) activity induced by 12-O-tetradecan oylphorbol 13-myristate (TPA) and markedly reduced levels of PKC alpha in N IH 3T3 fibroblasts. Furthermore, prolonged treatment with ELL-12 neither in hibited TPA-induced translocations of PKC alpha and PKC delta to the partic ulate fraction nor caused down-regulation, and did not affect the cellular distribution of TPA-insensitive PKC zeta. In Jurkat T cells, where ELL-12 m arkedly induced apoptosis that was blocked by an inhibitor of caspase-3-lik e activities, it had no effect on PKC activity or translocation induced by TPA. Thus, it seems unlikely that PKC is involved in the therapeutic effect s of ELL-12. (C) 1999 Federation of European Biochemical Societies.