Sensitization of BL cells to etoposide upon incubation with a lipid raft–disrupting agent. (A) S-100 cytosols from Raji cells pretreated with CB or MCD as detailed in the legend to Figure 6 were incubated for 30 minutes in the absence (▪) or presence (□) of cytochrome c and dATP, and caspase-3–like enzyme activity was determined by using the DEVD-AMC fluorogenic substrate. Data shown are mean values ± SDs (n = 4). (B) Raji BL cells were preincubated in the presence or absence of MCD for 1 hour prior to treatment with etoposide, and apoptosis was determined at the indicated time points by fluorescence microscopic evaluation of Hoechst 33342–labeled cells. Data are shown as mean values ± SDs (n = 3). (C) DG75 BL cells preincubated with MCD as in panel B, and then treated for 48 hours with etoposide prior to assessment of apoptosis. Data are shown as mean values ± SDs (n = 3). (D) Schematic model showing the apoptosis defect in BL-derived Raji cells, and the putative mechanism whereby lipid raft disruption sensitizes these cells to etoposide-induced killing. MCD indicates methyl-β-cyclodextrin.