Figure 2
Figure 2. Inhibition of Aurora kinase activity enhances p53-dependent apoptosis in AML cells. (A) AML cells were incubated with the indicated concentrations of MK-0457 for 48 hours, and the annexin V–positive fractions were measured by flow cytometry. Data are mean plus or minus SD. A dose-response relationship ranging from 5 to 100 nM was seen in MOLM-13 cells, whereas the effect reached the maximum at 10 nM in OCI-AML-3 and HL-60 cells. (B) Effects of MK-0457 and Nutlin-3 on viable cell number. Cells were incubated with a range of concentrations of Nutlin-3 in the absence or presence of 10 nM MK-0457 for 48 hours, and the cell viability was determined by the trypan blue exclusion method. Results are expressed as the percentage of the viable cell number in an untreated group and represent the average of triplicate cultures. (C) MK-0457 enhanced Nutlin-induced cytotoxicity in wild-type p53 OCI-AML-3 and MOLM-13 cells. Cells were incubated with a range of concentrations of Nutlin-3 in the absence or presence of 10 nM MK-0457 for 48 hours, and the cell viability was determined by the trypan blue exclusion method. Data are mean plus or minus SD. (D) MK-0457 enhanced Nutlin-induced apoptosis in wild-type p53 OCI-AML-3 and MOLM-13 cells but not in mutant p53 HL-60 cells. Cells were incubated with the indicated concentrations of MK-0457 or Nutlin-3, and the annexin V–positive fractions were measured by flow cytometry at 24 hours. Data are mean plus or minus SD.

Inhibition of Aurora kinase activity enhances p53-dependent apoptosis in AML cells. (A) AML cells were incubated with the indicated concentrations of MK-0457 for 48 hours, and the annexin V–positive fractions were measured by flow cytometry. Data are mean plus or minus SD. A dose-response relationship ranging from 5 to 100 nM was seen in MOLM-13 cells, whereas the effect reached the maximum at 10 nM in OCI-AML-3 and HL-60 cells. (B) Effects of MK-0457 and Nutlin-3 on viable cell number. Cells were incubated with a range of concentrations of Nutlin-3 in the absence or presence of 10 nM MK-0457 for 48 hours, and the cell viability was determined by the trypan blue exclusion method. Results are expressed as the percentage of the viable cell number in an untreated group and represent the average of triplicate cultures. (C) MK-0457 enhanced Nutlin-induced cytotoxicity in wild-type p53 OCI-AML-3 and MOLM-13 cells. Cells were incubated with a range of concentrations of Nutlin-3 in the absence or presence of 10 nM MK-0457 for 48 hours, and the cell viability was determined by the trypan blue exclusion method. Data are mean plus or minus SD. (D) MK-0457 enhanced Nutlin-induced apoptosis in wild-type p53 OCI-AML-3 and MOLM-13 cells but not in mutant p53 HL-60 cells. Cells were incubated with the indicated concentrations of MK-0457 or Nutlin-3, and the annexin V–positive fractions were measured by flow cytometry at 24 hours. Data are mean plus or minus SD.

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