I-BET726 treatment results in potent growth inhibition and cytotoxicity in neuroblastoma cell lines.

<p>(<b>a</b>) gIC₅₀ values observed for I-BET726 in a panel of neuroblastoma cell lines obtained from a 6 day growth-death assay. (<b>b</b>) Concentration response curves for SK–N-AS and CHP-212 from 6 day growth-death assay. Black horizontal line indicates growth in DMSO-treated controls. Red line indicates T₀ value (100%). gIC₅₀ and Y_min-T₀ values are indicated. Data presented as the average of two independent curves from a single experiment, and is representative of data from three independent biological replicates. (<b>c</b>) Y_min-T₀ values observed for I-BET726 in the panel of neuroblastoma cell lines obtained from a 6 day growth-death assay. Gray bars indicate a cytotoxic response, defined by a Y_min-T₀ value ≤ -50, with evidence of net cell death (Y < T₀) along the growth curve at concentrations less than 6 µM. (<b>d</b>) Graph summarizing number of cells in G1 phase (as a percent of total cell population) in the indicated neuroblastoma cell lines following treatment with a titration of I-BET726 (5 nM-20 000 nM) for 2 days based on propidium iodide staining. V represents vehicle (DMSO) control sample. (<b>e</b>) Histograms generated from cell cycle analysis in the CHP-212 cell line following 4 days treatment with the indicated concentration of I-BET726. Percentage of cells in G1 phase and sub-G1 phase are indicated. (<b>f</b>) Caspase induction in the indicated neuroblastoma cell lines following treatment with a titration of I-BET726 for one, two, or three days. Data is presented as fold induction over DMSO controls, following normalization to total cell number as measured by CellTiter-Glo.