Treatment of ex vivo-purified myeloma cells with lovastatin results in reduction of cell viability and induction of apoptosis by reducing Mcl-1 protein levels. Plasma cells from myeloma patient 1 were purified from bone marrow mononuclear cells by MACS based on CD138 expression. Plasma cell percentage was 97% after purification. Patient 2 had 96% myeloma cells in her bone marrow mononuclear cells; therefore, purification was not necessary. Tumor cells derived from patients 1 and 2 were treated for 4 days with solvent control or lovastatin (30 μM) alone or in the presence of mevalonate (meva; 100 μM), FOH (10 μM), or GGOH (10 μM). (A) The percentage of viable cells, relative to the solvent control-treated cells, was measured by using MTT assay. Experiments were performed once in triplicate. Data are presented as mean ± SEM. (B) The percentage of apoptotic cells was determined by the annexin V assay. The percentages of viable myeloma cells (annexin V-/PI-), early apoptotic cells (annexin V+/PI-), and late apoptotic cells (annexin V+/PI+) in each dot plot are indicated in the corresponding quadrants. (C) After protein isolation, Mcl-1, Bcl-XL, Bcl-2, and Bax expression levels were determined by Western blot analysis. Furthermore, the proapoptotic 23-kDa Bcl-2 form was detected after long exposure of the film.