Cytotoxic effects of GF109203X, a dual inhibitor of protein kinase C (IC₅₀, ∼ 0.1μM) and of GRK6 (IC₅₀, ∼ 1-10μM), on myeloma cells versus nonmyeloma cells. (A) Cytotoxicity of 20μM GFX109203X at 72 hours is summarized for a spectrum of human myeloma and nonmyeloma cells, with statistical comparison by Mann-Whitney test. (B) An illustrative example of selective cytotoxic effect of GF109203X versus primary myeloma cells in mixed culture. Primary bone marrow cells from myeloma patients were treated in culture with 1.25 to 20μM GF109203X, or with dimethyl sulfoxide (DMSO) vehicle control. After 72 hours, samples were stained with CD138–fluorescein isothiocyanate to identify myeloma cells (bottom right population) versus other marrow cells (bottom left population) and propidium iodide to distinguish late-stage apoptotic cells. At high concentrations (reflective of GRK6 rather than protein kinase C effect), GF109203X induced selective cytotoxicity that was confined to the tumor cell population, evidenced by CD138 shedding and propidium iodide uptake.