DS-7423–mediated induction of apoptosis in ovarian clear cell adenocarcinoma cell lines.

<p>(A) All nine OCCA cells were treated with DS-7423 at 156 or 2,560 nM for 48 h, and apoptotic cell proportion was evaluated using annexin-V fluorescein isothiocyanate (FITC) and propidium iodide (PI) double staining, followed by analysis using flow cytometry. The experiments were repeated 3 times, and each value is shown as the mean of 3 experiments ± standard deviation (SD). (B) The apoptotic cells were calculated using flow cytometry by counting the cell population in the right boxes. The example shown (OVISE cells) is representative of the results obtained for all the cell lines tested. (C) The proportion of cells rendered apoptotic by exposure to DS-7423 at 156 nM and 2,560 nM was significantly higher in OCCA cells without mutations in TP53 than in OCCA cells that carry mutations in TP53. (D) Cleaved poly(ADP-ribose) polymerase (PARP) induction was evaluated by immunoblotting in OVISE cells. OVISE cells were treated with DS-7423 at 156 nM for the times indicated (left) or for 4 h at the doses indicated (right).