Ceramide-induced apoptosis in Fas-resistant Hodgkin's disease cell lines is caspase independent

We investigated whether cell-permeable, synthetic ceramide (C6 ceramide) co uld induce apoptosis in Fas-resistant Hodgkin's disease (HD)-derived cell l ines. Despite strongly expressing the Fas-receptor, two of three HD-derived cell lines were resistant to Fas-mediated apoptosis, This resistance to Fa s could not be attributed to differential Fas isoform generation patterns b etween the Fas-resistant and the Fas-sensitive cell lines, The Fas-resistan t cell lines did not demonstrate the presence of Fas exon 8 deletion. Bcl-2 and BclxL levels were comparable between the Fas-resistant and the Fas-sen sitive cell lines, C6 ceramide could induce apoptosis in both Fas-resistant cell lines and this was associated with a decrease in BclxL level. Caspase -1, caspase-3, or pan-caspase inhibitors could not prevent ceramide-induced apoptosis, Furthur, ceramide treatment did not lead to cleavage of caspase 3 or poly(ADP-ribose) polymerase, but caused a loss in mitochondrial trans membrane potential which could not be prevented by caspase inhibitors. Thus , we conclude that ceramide-induced apoptosis in Fas-resistant HD cell line s is caspase independent. (C) 2000 Academic Press.