title: The anti-cancer drug etoposide can induce caspase-8 processing and apoptosis in the absence of CD95 receptor-ligand interaction.
abstract: Caspase-8 (FLICE) can associate with and be activated by CD95 (APO-1/Fas), an apoptosis-inducing member of the Tumour Necrosis Factor receptor family. We find that, in Jurkat T cells, the DNA damaging anti-cancer drug etoposide induces apoptosis and, surprisingly, processing of caspase-8. Therefore, we have investigated whether etoposide involves CD95 receptor activation. We find that etoposide does not induce CD95 ligand expression at the mRNA level. In addition, blocking of CD95 receptor function with a specific antibody does not inhibit etoposide-induced apoptosis. Apparently, in Jurkat cells, etoposide can induce caspase-8 processing and apoptosis in a CD95-independent fashion. Likewise, we find that thymocytes from the CD95-deficient lpr/lpr mouse strain readily undergo apoptosis in response to etoposide. Moreover, since inhibition of the secretory pathway with brefeldin A does not inhibit etoposide-induced apoptosis, we exclude the requirement for a newly synthesized receptor ligand to induce the apoptotic pathway. We conclude that, at least in certain cell types, etoposide does not require CD95 receptor function to induce caspase-8 processing and apoptosis.
authors.affiliation: Division of Cellular Biochemistry, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands.
authors.forename: J G
authors.initials: JG
authors.lastname: Boesen-de Cock
authors.forename: E
authors.initials: E
authors.lastname: de Vries
authors.forename: G T
authors.initials: GT
authors.lastname: Williams
authors.forename: J
authors.initials: J
authors.lastname: Borst