okadaic-acid and Hodgkin-Disease

We investigated whether cell-permeable, synthetic ceramide (C6 ceramide) could induce apoptosis in Fas-resistant Hodgkin's disease (HD)-derived cell lines. Despite strongly expressing the Fas-receptor, two of three HD-derived cell lines were resistant to Fas-mediated apoptosis. This resistance to Fas could not be attributed to differential Fas isoform generation patterns between the Fas-resistant and the Fas-sensitive cell lines. The Fas-resistant 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-sensitive 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 transmembrane potential which could not be prevented by caspase inhibitors. Thus, we conclude that ceramide-induced apoptosis in Fas-resistant HD cell lines is caspase independent.

Topics: Amino Acid Chloromethyl Ketones; Apoptosis; bcl-X Protein; Caspase 1; Caspase 3; Caspase Inhibitors; Caspases; CD40 Antigens; Cell Membrane Permeability; Ceramides; Cysteine Proteinase Inhibitors; Enzyme Inhibitors; Fas Ligand Protein; fas Receptor; Gene Expression; Hodgkin Disease; Humans; Membrane Glycoproteins; Okadaic Acid; Oligopeptides; Poly(ADP-ribose) Polymerases; Proto-Oncogene Proteins c-bcl-2; Tetradecanoylphorbol Acetate; Tumor Cells, Cultured; Up-Regulation