TY - JOUR T1 - Inhibition of P-TEFb by DRB Suppresses SIRT1/CK2α Pathway and Enhances Radiosensitivity of Human Cancer Cells JF - Anticancer Research JO - Anticancer Res SP - 6981 LP - 6989 VL - 34 IS - 12 AU - ZHI-QIANG WANG AU - CASEY L. JOHNSON AU - AMIT KUMAR AU - DAVID P. MOLKENTINE AU - JESSICA M. MOLKENTINE AU - TATIANA RABIN AU - KATHRYN A. MASON AU - LUKA MILAS AU - UMA RAJU Y1 - 2014/12/01 UR - http://ar.iiarjournals.org/content/34/12/6981.abstract N2 - Background: Positive transcription elongation factor-b (P-TEFb) is a complex containing CDK9 and a cyclin (T1, T2 or K). The effect of inhibition of P-TEFb by 5,6-dichloro-l-β-D-ribofuranosyl benzimidazole (DRB) on cell radiosensitivity and the underlying mechanisms were investigated. Materials and Methods: Six human cancer cell lines were subjected to 3H-uridine incorporation, cell viability and clonogenic cell survival assays; cell-cycle redistribution and apoptosis assay; western blots and nuclear 53BP1 foci analysis after exposing the cells to DRB with/without γ-radiation. Results: DRB suppressed colony formation and enhanced radiosensitivity of all cell lines. DRB caused a further increase in radiation-induced apoptosis and cell-cycle redistribution depending on p53 status. DRB prolonged the presence of radiation-induced nuclear p53 binding protein-1 (53BP1) foci and suppressed the expression of sirtuin-1 (SIRT1) and casein kinase 2-alpha (CK2α), suggesting an inhibition of DNA repair processes. Conclusion: Our findings indicate that DRB has the potential to increase the efficacy of radiotherapy and warrants further investigation using in vivo tumor models. ER -