TY - JOUR T1 - Aurora B Inhibitor TAK-901 Synergizes with BCL-xL Inhibition by Inducing Active BAX in Cancer Cells JF - Anticancer Research JO - Anticancer Res SP - 437 LP - 444 VL - 37 IS - 2 AU - SAOMI MURAI AU - JENNIFER MATUSZKIEWICZ AU - YUUMI OKUZONO AU - HIROYUKI MIYA AU - RON DE JONG Y1 - 2017/02/01 UR - http://ar.iiarjournals.org/content/37/2/437.abstract N2 - Background: Aurora B kinase plays an essential role in chromosome segregation and cytokinesis, and is dysregulated in many cancer types, making it an attractive therapeutic target. TAK-901 is a potent aurora B inhibitor that showed efficacy in both in vitro and in vivo oncology models. Materials and Methods: We conducted a synthetic lethal siRNA screening to identify the genes that, when silenced, can potentiate the cell growth-inhibitory effect of TAK-901. Results: B-cell lymphoma-extra large (BCL-xL) depletion by siRNA or chemical inhibition synergized with TAK-901 in cancer cell lines. As a mechanism of synthetic lethality, active BCL2 associated X, apoptosis regulator (BAX) was induced by TAK-901. BCL-xL protected cells from BAX-dependent apoptosis induction. Therefore, TAK-901 sensitizes cancer cells to BCL-xL inhibition. Conclusion: Polyploid cells induced by TAK-901 are vulnerable to BCL-xL inhibition. Our findings may have an impact on combination strategies with aurora B inhibitors in clinical studies. ER -