Activation of the CD95 (APO-1/Fas) pathway in drug- and γ-irradiation-induced apoptosis of brain tumor cells

摘要: Chemotherapeutic agents and γ-irradiation used in the treatment of brain tumors, most common solid tumors childhood, have been shown to act primarily by inducing apoptosis. Here, we report that activation CD95 pathway was involved drug- γ-irradiation-induced apoptosis medulloblastoma glioblastoma cells. Upon ligand (CD95-L) induced stimulated crosslinking via an autocrine/paracrine loop. Blocking CD95-L/receptor interaction using F(ab′)2 anti-CD95 antibody fragments strongly reduced Apoptosis depended on caspases (interleukin 1β-converting enzyme/Ced-3 like proteases) as it almost completely abrograted broad range caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone. mediated cleavage receptor proximal FLICE/MACH (caspase-8) downstream CPP32 (caspase-3, Apopain) resulting prototype substrate PARP. Moreover, upregulated wild-type p53 cells thereby increasing responsiveness towards triggering. Since system upon also found primary ex vivo, these findings may implications define chemosensitivity develop novel therapeutic strategies management malignant tumors.