Specific inhibition of phorbol diester-induced granulocyte-macrophage progenitor cell (GM-CFU) differentiation by lipoxygenase inhibitors.
The induction of differentiation of SENCAR murine granulocyte-macrophage precursor cells (GM-CFU) by the tumor-promoting phorbol diester 12-O--tetradecanoyl-phorbol-13-acetate (TPA) was inhibited by agents reported to inhibit specific aspects of arachidonic acid metabolism. These agents included phospholipase A2 inhibitors, and eicosatetraynoic acid (ETYA), a competitive inhibitor of arachidonic acid oxygenases. Whereas inhibitors reported specific for lipoxygenases were also active, no comparable effect was observed for inhibitors of the corresponding cyclooxygenase. These findings are therefore consistent with the hypothesis that induced differentiation of GM-CFU cells is regulated by products of arachidonic acid metabolism formed principally via lipoxygenase activity.
D015117:5,8,11,14-Eicosatetraynoic Acid / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000502:physiology*; D001205:Ascorbic Acid / Q000494:pharmacology; D002083:Butylated Hydroxyanisole / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects*; D003114:Colony-Forming Units Assay; D003907:Dexamethasone / Q000494:pharmacology; D006098:Granulocytes / Q000166:cytology*; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D007052:Ibuprofen / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology*; D016859:Lipoxygenase Inhibitors; D008264:Macrophages / Q000166:cytology*; D009637:Masoprocol / Q000494:pharmacology; D051379:Mice; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D001095:Arachidonic Acids; D016859:Lipoxygenase Inhibitors; D015117:5,8,11,14-Eicosatetraynoic Acid; D002083:Butylated Hydroxyanisole; D016718:Arachidonic Acid; D009637:Masoprocol; D003907:Dexamethasone; D013755:Tetradecanoylphorbol Acetate; D001205:Ascorbic Acid; D007052:Ibuprofen; D007213:Indomethacin