Inhibition of proliferation of myeloma cell lines as well as survival of primary myeloma cells and cells of the bone marrow microenvironment. (Ai) Inhibition of proliferation of 20 myeloma cell lines by the pan-aurora kinase inhibitor VX680 in graded concentrations versus medium and DMSO controls, respectively, measured by ³H-thymidine uptake. Two independent experiments were performed in triplicate. (Aii) The IC₅₀ (in micromolarity) and maximal inhibition at 10 μM (IMAX10 expressed as a percentage) are shown. (Bi) Survival of primary myeloma cells (pMMCs) cultured within their bone marrow microenvironment (negative fraction of plasma cell purification) is significantly inhibited compared with the medium control, as determined by staining with anti-CD138-FITC antibody and propidium iodine. An asterisk (*) indicates a significant decrease between the medium control and the respective VX680 concentration. (Bii) Survival of cells within the bone marrow microenvironment (BMME cells; negative fraction of plasma cell purification) was determined as described above for pMMC. An asterisk (*) indicates a significant decrease between the medium control and the respective VX680 concentration. (C) Induction of apoptosis by VX680 at 1 μM as determined by annexin V staining after 8, 24, 48, and 72 hours.