American Society of Hematology

Figure 1.

$Figure 1. Bay 11-7082 interacts synergistically with UCN-01 to induce apoptosis in MM cells. (A-B) U226 MM cells were treated with various concentrations of Bay 11-7082 (A, 2-10 μM) and UCN-01 (B, 100-500 nM) for the indicated intervals (24-72 hours), after which the percentage of apoptotic cells was determined by evaluating Wright-Giemsa-stained cytospin preparations, as described in “Materials and methods.” Values represent means ± SDs for 3 separate experiments. (C) U266 cells exposed to 4 μM Bay 11-7082 ± 200 nM UCN-01 for 24 hours, after which annexin V-FITC staining and flow cytometric analysis were performed to monitor the extent of apoptosis, as described in “Materials and methods.” For each histogram, the lower right quadrant (annexin V+/PI-) represents early apoptosis; the upper right quadrant (annexin V+/PI+) represents late apoptosis. Numbers indicate the percentage of cells in the corresponding quadrant. Two additional experiments yielded equivalent results. (D) U266 cells were exposed to a range of Bay 11-7082 (3-4.5 μM) and UCN-01 (150-225 nM) concentrations alone and in combination at a fixed ratio (20:1) for 24 hours. At the end of this period, the percentage of apoptotic cells was determined for each condition; fractional effect values were determined by comparing results with those of untreated controls, and median dose effect analysis was used to characterize the nature of the interaction between Bay 11-7082 and UCN-01. Combination index (C.I.) values less than 1.0 (horizontal dotted line) denote a synergistic interaction. Two additional studies yielded equivalent results. (E) U266 cells were treated as described in panel C for the indicated intervals (24-72 hours), after which the percentage of apoptotic cells was determined by evaluating Wright-Giemsa-stained cytospin preparations. Values represent means ± SDs for 3 separate experiments performed in triplicate. (F) Dexamethasone-sensitive (MM.1S) and -resistant (MM.1R) human MM cell lines were exposed to 1 μM Bay 11-7082 ± 200 nM UCN-01 for 24 hours, after which the percentage of apoptotic cells was determined as described above. Values represent means ± SDs for 3 separate experiments performed in triplicate.$

Bay 11-7082 interacts synergistically with UCN-01 to induce apoptosis in MM cells. (A-B) U226 MM cells were treated with various concentrations of Bay 11-7082 (A, 2-10 μM) and UCN-01 (B, 100-500 nM) for the indicated intervals (24-72 hours), after which the percentage of apoptotic cells was determined by evaluating Wright-Giemsa-stained cytospin preparations, as described in “Materials and methods.” Values represent means ± SDs for 3 separate experiments. (C) U266 cells exposed to 4 μM Bay 11-7082 ± 200 nM UCN-01 for 24 hours, after which annexin V-FITC staining and flow cytometric analysis were performed to monitor the extent of apoptosis, as described in “Materials and methods.” For each histogram, the lower right quadrant (annexin V⁺/PI^-) represents early apoptosis; the upper right quadrant (annexin V⁺/PI⁺) represents late apoptosis. Numbers indicate the percentage of cells in the corresponding quadrant. Two additional experiments yielded equivalent results. (D) U266 cells were exposed to a range of Bay 11-7082 (3-4.5 μM) and UCN-01 (150-225 nM) concentrations alone and in combination at a fixed ratio (20:1) for 24 hours. At the end of this period, the percentage of apoptotic cells was determined for each condition; fractional effect values were determined by comparing results with those of untreated controls, and median dose effect analysis was used to characterize the nature of the interaction between Bay 11-7082 and UCN-01. Combination index (C.I.) values less than 1.0 (horizontal dotted line) denote a synergistic interaction. Two additional studies yielded equivalent results. (E) U266 cells were treated as described in panel C for the indicated intervals (24-72 hours), after which the percentage of apoptotic cells was determined by evaluating Wright-Giemsa-stained cytospin preparations. Values represent means ± SDs for 3 separate experiments performed in triplicate. (F) Dexamethasone-sensitive (MM.1S) and -resistant (MM.1R) human MM cell lines were exposed to 1 μM Bay 11-7082 ± 200 nM UCN-01 for 24 hours, after which the percentage of apoptotic cells was determined as described above. Values represent means ± SDs for 3 separate experiments performed in triplicate.

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