NVP-LAQ824 causes apoptosis in human myeloma cell lines (HMCLs) resistant to conventional chemotherapy. (A-C) The effect of NVP-LAQ824 on DNA synthesis in MM cell lines was determined by measuring ³H-thymidine uptake during the last 8 hours of 48-hour cultures, in the presence or absence of drug at various concentrations. (A) Proliferation of MM.1R cells resistant to Dex was unaffected by culture with 1 μM Dex (dotted line), but was completely inhibited by less than 1.0 μM NVP-LAQ824 (solid line). (B-C) RPMI 8226 MM cells resistant to Dox (Dox40 cells), Mit (MR20 cells), or Mel (LR5 cells) were inhibited in a dose-dependent manner by NVP-LAQ824 at concentrations of 0 (□), 10 nM (▪), 100 nM (▤), and 1 μM (), as demonstrated by thymidine uptake and MTS assay. Error bars represent ± 1 SD of a triplicate experiment. (D) Percent of annexin-positive HMCLs (▪), RPMI 8226, U266, MM.1S and dexamethasone-resistant MM.1R cells were quantitated after 24-hour incubation with 0.01 to 1 μM NVP-LAQ824.