Which cell-death pathways are activated by rATG in CD138+ myeloma cells?
In previous work with CD40L-activated human B cells, we found that rATG triggered caspase-dependent and cathepsin D-dependent cell-death pathways. Myeloma cells are known to vary in their sensitivity to various proapoptotic stimuli and pathways, and we therefore asked which of several apoptosis pathway inhibitors could prevent rATG-induced myeloma-cell death (Table 1). Significant reductions in rATG-triggered apoptosis were observed with the cathepsin D inhibitor pepstatin A in NCI-H929 and ARH-77 lines, and with tyrosine kinase inhibitor genistein in NCI-H929 and U266 myeloma cell lines. Modest reductions in apoptosis were seen in the RPMI-8226 and U266 cell lines with the pancaspase inhibitor z-VAD-fmk. In contrast to our findings in CD40L-stimulated human B cells (sBc’s), the inhibitor of lysosomal cysteine proteases (E64d) cathepsins B and D had no effect on rATG-induced apoptosis.
