Figure 1.
BAY 1143572 inhibits proliferation, induces apoptosis, and affects CDK9 signaling in ATL-derived or HTLV-1–transformed cell lines. (A) Viabilities of ATL-derived or HTLV-1–transformed cell lines in the presence of different concentrations of BAY 1143572 for 72 hours (ATN-1, MJ, MT-1, MT-2, TL-Om1, TL-Su, and MT-4) and 24 hours (S-YU) were assessed. S-YU cells were assessed in the presence of recombinant human IL-2 at a final concentration of 100 IU/mL. The IC50 value (the concentration of inhibitor where the response is reduced by half the maximal value) for each line is indicated in each panel. The absolute IC50 value (the concentration of an inhibitor that reduced cell survival to 50% of the untreated control value, with the highest observed viability [no inhibitor] defined as 100%, and the lowest viability defined as 0%) for each line is also indicated in parentheses below the IC50 value. (B) ATL-derived or HTLV-1–transformed cell lines were treated with various concentrations of BAY 1143572 for 72 hours. Apoptosis was then analyzed by Annexin V and propidium iodide (PI; nuclear) staining and flow cytometry. BAY 1143572 concentrations are indicated above the panels, and the percentage of cells in each quadrant is indicated in or beside each quadrant. (C) ATN-1, TL-Om1, MT-4, and MJ cell lines were treated with the indicated concentrations of BAY 1143572 for 5 hours, and western blotting was performed. Blots were probed with antibodies to phospho-RNAPII (Ser2 of the CTD [Ser2]), phospho-RNAPII (Ser5), RNAPII (N-20), c-Myc, Mcl-1, and HTLV-1 Tax. Actin was used as a loading control.