Lipoxygenase inhibitors block CD95 ligand-mediated apoptosis of human malignant glioma cells.
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.
Wagenknecht
B
B
Department of Neurology, University of Tübingen, School of Medicine, Germany.
Gulbins
E
E
Lang
F
F
Dichgans
J
J
Weller
M
M
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*
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