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Cancer Res. 2004, 64:7144 7149. 23. Mahrhofer H, Burger S, Oppitz U, Flentje M, Djuzenova CS. Radiation induced DNA damage and damage repair in human tumor and fibroblast cell lines assessed by histone H2AX phosphorylation. Int J Radiat Oncol Biol Phys. 2006, 64:573 580. 24. Riches LC, Lynch AM, Gooderham NJ. Early events in the mammalian response to DNA doublestrand breaks. Mutagenesis. 2008, 23:331 339. 25. Addepalli MK, Ray KB, Kumar B, Ramnath RL, Chile S, Rao H. RNAi mediated knockdown of AURKB and EGFR shows enhanced therapeutic efficacy in prostate tumor regression. Gene Ther. 2010, 17:352 359. Niermann et al. Page 9 Radiat Res. Author manuscript, available in PMC 2012 April 1. NIH PA Author Manuscript NIH PA Author Manuscript NIH PA Author Manuscript FIG. 1.
AZD1152 treatment of PC3 and DU145 prostate cancer cells results in stable expression of AURKB but decreased levels of phosphorylated histone H3, with increasing effect with escalation of concentration and treatment duration. Panel A: PC3 and DU145 cells were treated with various concentrations of AZD1152 for 48 h, with subsequent immunoblotting analysis. β Actin was probed as a positive control to demonstrate equal loading. Panel B: PC3 and DU145 cells were treated with 60 nM AZD1152 for various treatment times. Niermann et al. Page 10 Radiat Res. Author manuscript, available in PMC 2012 April 1. NIH PA Author Manuscript NIH PA Author Manuscript NIH PA Author Manuscript FIG. 2. AZD1152 induces G2/M and polyploidy cell cycle arrest in PC3 and DU145 prostate cancer cells in a dose responsive and treatment time responsive manner.
Panel A: PC3 and DU145 cells were treated with increasing concentrations of AZD1152 for 48 h. Panel B: PC3 cells and DU145 cells were treated 60 nM AZD1152 for increasing treatment durations. Cell numbers in each of the cell cycle phases were determined using flow cytometry. Niermann et al. Page 11 Radiat Res. Author manuscript, available in PMC 2012 April 1. NIH PA Author Manuscript NIH PA Author Manuscript NIH PA Author Manuscript FIG. 3. AZD1152 increases radiation induced DNA damage and reduces DNA damage repair processes in PC3 and DU145 cells. The results for four treatment groups are shown: AZD1152 t followed by radiation , radiation alone, AZD1152 alone, no radiation and no AZD1152. γ H2AX was used to measure DNA damage. The means ± SD of thre