pp242 is more effective than rapamycin against MM cell lines. (A) Four cell lines were treated with increasing concentrations of rapamycin (x) or pp242 (o) for 72 hours and number of recovered viable cells was assessed. Data presented as percent of control (no inhibitor treatment), mean of triplicate samples. The standard deviation (SD) in all groups was < 5% of the mean. (B) Similarly treated MM cell lines were assessed for induction of apoptosis by flow cytometric analysis for expression of activated caspase 3. Data represent percent apoptosis over control (no inhibitor treatment), mean of triplicate samples. The SD was < 5% of the mean in all groups. Rapamycin treatment represented by dark bars and pp242 represented by white bars. (C) MM1.S cells treated with 0, 250, 500, or 1000nM pp242 and apoptosis assayed by annexin V staining. Percents shown are percent annexin V-positive cells. (D) 8226 MM cells treated for 48 hours ± IGF-1 (250 ng/mL) with increasing concentrations of either rapamycin or pp242 and apoptosis assayed by activated caspase 3 staining (open bars) and annexin V staining (black bars). (E) NOD/SCID mice were challenged with SC 8226 MM cells and treated with daily intraperitoneal injections of pp242 at 20 mg/kg for 8 treatments or vehicle alone (control). Treatment started when tumors were 200 mm³. The data represent the mean ± SD volume of pp242-treated tumors versus control (N = 6). The pp242-treated tumor volumes are significantly (P < .05) lower than that of control mice.