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.