Tipifarnib enhances induction of apoptosis by etoposide in AML cell lines. (A) Log-phase HL-60 cells were treated for 24 hours with diluent, 1.5 μM etoposide, 1 μM tipifarnib, or the combination of 1.5 μM etoposide plus 1 μM tipifarnib. At the completion of the incubation, cells were fixed, stained with Hoechst 33258, and examined by fluorescence microscopy. Arrow represents apoptotic cells. (B) Samples shown in panel A and additional samples treated with differing concentrations of etoposide in the absence or presence of 1 μM tipifarnib were examined by fluorescence microscopy (> 500 cells/sample) by an investigator blinded to the treatment, and the percentage of cells displaying apoptotic morphologic changes was recorded. Inset in panel B: summary of 4 independent experiments in which HL-60 cells were treated with diluent, 2 μM etoposide, 1 μM tipifarnib, or 2 μM etoposide plus 1 μM tipifarnib. Error bars represent ± 1 SD. *P = .015 by paired t test. (C) Log-phase U937 cells were treated for 24 hours with diluent, 0.375 μM etoposide, 1 μM tipifarnib, or the combination of 0.375 μM etoposide plus 1 μM tipifarnib. At the completion of the incubation, cells were permeabilized, stained with propidium iodide, and examined by flow microfluorimetry. (D) Samples shown in panel C and additional samples treated with differing concentrations of etoposide in the absence or presence of 1 μM tipifarnib were examined by flow cytometry, and the percentage of cells with less than 2n DNA content was recorded. (D inset) Summary of 4 independent experiments in which U937 cells were treated with diluent, 0.375 μM etoposide, 1 μM tipifarnib, or 0.375 μM etoposide plus 1 μM tipifarnib. Error bars represent ± 1 SD. *P = .008 by paired t test.