title: Lipoxygenase inhibitors block CD95 ligand-mediated apoptosis of human malignant glioma cells.
abstract: CD95 ligand is a cytotoxic cytokine that induces apoptosis. Here we report that CD95-mediated apoptosis of human malignant glioma cells is associated with arachidonic acid (AA) release. Inhibitors of phospholipase A2, phospholipase C or diacylglycerol lipase have minor effects on AA release and fail to modulate apoptosis. Formation of two AA metabolites generated during CD95-dependent apoptosis is attenuated by the lipoxygenase inhibitor, nordihydroguaretic acid (NDGA). NDGA also blocks CD95 ligand-induced apoptosis. This effect is independent of antioxidant properties of NDGA. Lipoxygenase may thus play a critical role in CD95 ligand-induced apoptosis of human malignant glioma cells.
authors.affiliation: Department of Neurology, University of Tübingen, School of Medicine, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Wagenknecht
authors.forename: E
authors.initials: E
authors.lastname: Gulbins
authors.forename: F
authors.initials: F
authors.lastname: Lang
authors.forename: J
authors.initials: J
authors.lastname: Dichgans
authors.forename: M
authors.initials: M
authors.lastname: Weller
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000276:immunology*; D016718:Arachidonic Acid / Q000378:metabolism; D053222:Fas Ligand Protein; D005910:Glioma / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D006801:Humans; D008024:Ligands; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology*; D009637:Masoprocol / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D010740:Phospholipases / Q000037:antagonists & inhibitors; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000378:metabolism*
chemical_list: C505661:FASLG protein, human; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008024:Ligands; D016859:Lipoxygenase Inhibitors; D008562:Membrane Glycoproteins; D019014:fas Receptor; D016718:Arachidonic Acid; D009637:Masoprocol; D010740:Phospholipases