STIMULATION BY RETINOIC ACID OF PROSTAGLANDIN PRODUCTION AND ITS INHIBITION BY TUMOR PROMOTERS IN MOUSE MYELOID-LEUKEMIA CELLS

  • 1 January 1981
    • journal article
    • research article
    • Vol. 72  (4) , 488-497
Abstract
Retinoic acid induced lysozyme activity in mouse myeloid leukemia M1 cells. It also stimulated the synthesis and release of prostaglandins [PG] such as PG F2.alpha., E2, and PGD2 by the cells. The particulate fraction of retinoic acid-treated M1 cells converted archidonate to PG and this conversion was almost completely inhibited by indomethacin. Retinol, retinal and retinyl acetate, but not the pyridyl analog of retinoic acid, also induced lysozyme activity and stimulated synthesis and release of PG. Indomethacin inhibited the induction of lysozyme activity by retinoic acid. The induction of lysozyme activity and the stimulation of PGE2 production were dependent on the concentration of retinoic acid. Kinetic studies showed that stimulation of PGE2 production by retinoic acid was followed by induction of lysozyme activity. The tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate (TPA) and phorbol 12,13-didecanoate inhibited the induction of lysozyme activity by retinoic acid, but 4.alpha.-phorbol didecanoate and phorbol did not. TPA and phorbol 12,13-didecanoate, but not 4.alpha.-phorbol didecanoate, also inhibited the stimulation of PGE2 production by retinoic acid. Stimulation by retinoic acid of PGE2 production in M1 cells may be a prerequisite for the induction of lysozyme activity. Retinoic acid and TPA inhibited the induction by dexamethasone of phagocytic activity, which is a typical functional marker of differentiation of M1 cells, without causing significant growth inhibition. Suboptimal concentrations of retinoic acid and TPA had synergistic inhibitory effects on the induction of phagocytic activity of M1 cells by dexamethasone.