Targeting p53-MDM 2 interaction in pediatric ALL

Introduction: The tumor suppressor p53 is a key regulator of cell cycle and apoptosis in cancer. The small molecule RITA interferes with MDM 2-p53 interaction resulting in p53 accumulation and cell death induction. Methods: Apoptosis estimation by AnnexinV/PI, expression of p53 targets by western blotting, shRNA mediated p53-knock down. Results: RITA induced apoptosis including up-regulation of p53 downstream targets PUMA and NOXA in (TP53wt) ALL cells. Combinatorial exposure to the DNA-damaging agent doxorubicin and RITA revealed synergistic effectivity. Surprisingly, down-regulation of p53 did not change the s…