HIV-1 protease inhibitors decrease proliferation and induce differentiation of human myelocytic leukemia cells by Takayuki Ikezoe, Eric S. Daar, Jun-ichi Hisatake, Hirokuni Taguchi, and H. Phillip Koeffler Blood Volume 96(10):3553-3559 November 15, 2000 ©2000 by American Society of Hematology

Proliferation of HL-60 and NB 4 cells Proliferation of HL-60 and NB 4 cells.Dose-response effects of indinavir, ritonavir, and saquinavir on proliferation of HL-60 (A) and NB4 (B) cells are shown. Proliferation of HL-60 and NB 4 cells.Dose-response effects of indinavir, ritonavir, and saquinavir on proliferation of HL-60 (A) and NB4 (B) cells are shown. Results are expressed as a percent of control plates containing no protease inhibitor. Data represent mean ± SD of triplicate cultures. These figures show findings of at least 3 independent experiments. ■, indinavir; ⋄, ritonavir; ○, saquinavir. Takayuki Ikezoe et al. Blood 2000;96:3553-3559 ©2000 by American Society of Hematology

Proliferation of HL-60, NB4, and UF-1 cells Proliferation of HL-60, NB4, and UF-1 cells.The effects of the combination of ATRA and HIV-1 protease inhibitors on proliferation of HL-60 (A), NB4 (B), and UF-1 (C) are shown. Proliferation of HL-60, NB4, and UF-1 cells.The effects of the combination of ATRA and HIV-1 protease inhibitors on proliferation of HL-60 (A), NB4 (B), and UF-1 (C) are shown. Cells were cultured with various concentrations of ATRA (10−8-10−6 mol/L for HL-60 and UF-1; 10−11-10−9 mol/L for NB4) either alone or in combination with indinavir (2 × 10−5 mol/L), ritonavir (1 × 10−5 mol/L), or saquinavir (1 × 10−5 mol/L). Data represent mean ± SD of triplicate cultures and results represent at least 3 independent experiments. ■, ATRA; ⋄, ATRA + Indinavir (2 × 10-5 mol/L; ○, ATRA + Ritonavir (1 × 10-5 mol/L); ▵, ATRA + Saquinavir (1 × 10-5 mol/L). Takayuki Ikezoe et al. Blood 2000;96:3553-3559 ©2000 by American Society of Hematology

Effects of HIV-protease inhibitors on CD11b expression of HL-60 cells and CD66b expression on NB4 cells.(A) HL-60 cells were cultured for 5 days with either ATRA (10−11-10−9 mol/L) alone or in combination with either indinavir (2 × 10−5 mol/L), ritonavir (1... Effects of HIV-protease inhibitors on CD11b expression of HL-60 cells and CD66b expression on NB4 cells.(A) HL-60 cells were cultured for 5 days with either ATRA (10−11-10−9 mol/L) alone or in combination with either indinavir (2 × 10−5 mol/L), ritonavir (1 × 10−5 mol/L), or saquinavir (1 × 10−5 mol/L), and then analyzed by FACscan for expression of CD11b. (B) NB4 cells were cultured for 5 days with either ATRA (10−10-10−9 mol/L) alone or in combination with indinavir (2 × 10−5 mol/L), ritonavir (0.5 × 10−5 mol/L), or saquinavir (0.5 × 10−5 mol/L), and then analyzed by FACscan for expression of CD66b. These results represent 3 independent experiments. Takayuki Ikezoe et al. Blood 2000;96:3553-3559 ©2000 by American Society of Hematology

NBT reduction.The effects of HIV-1 protease inhibitors on NBT reduction of HL-60 (A) and NB4 (B) are shown. NBT reduction.The effects of HIV-1 protease inhibitors on NBT reduction of HL-60 (A) and NB4 (B) are shown. Cells were cultured for 5 days with various concentrations of ATRA (10−8-10−7 mol/L for HL-60; 10−10-10−9 mol/L for NB4) either alone or in combination with either indinavir (2 × 10−5mol/L), ritonavir (1 × 10−5 mol/L), or saquinavir (1 × 10−5 mol/L), and differentiation was determined by NBT reduction. Figure shows results of 3 independent experiments. Takayuki Ikezoe et al. Blood 2000;96:3553-3559 ©2000 by American Society of Hematology

Enhancement of C/EBPε mRNA expression in NB4 cells by indinavir Enhancement of C/EBPε mRNA expression in NB4 cells by indinavir.NB4 cells were cultured for 48 hours under various conditions: lane 1, (diluent control); lane 2, indinavir (2 × 10−5 mol/L); lane 3, ATRA (10−9 mol/L); lane 4, combination of indinavir (2 × 10... Enhancement of C/EBPε mRNA expression in NB4 cells by indinavir.NB4 cells were cultured for 48 hours under various conditions: lane 1, (diluent control); lane 2, indinavir (2 × 10−5 mol/L); lane 3, ATRA (10−9 mol/L); lane 4, combination of indinavir (2 × 10−5 mol/L) and ATRA (10−9mol/L). Total RNA was extracted and analyzed by Northern blot technique (30 μg/lane) and hybridized with [32P]-labeled C/EBPε cDNA probe as described in “Materials and methods.” The same blot was rehybridized with [32P]-labeled GAPDH probe to show equality of RNA loading in each lane. Results are expressed as fold increase in expression as compared with control NB4 cells (lane 1). The band intensity was measured using a densinometer. Takayuki Ikezoe et al. Blood 2000;96:3553-3559 ©2000 by American Society of Hematology