Dynamics of caspase activation upon UV induced genotoxic injury

Purpose Caspases are common mediators of cell death. Evasion death including apoptosis considered to be hallmarks cancer. A deeper understanding the apoptotic cascade may aid improving cancer therapies. Our aim was characterize progression following UV-induced genotoxic injury in a defined culture model.Materials and methods Hela cells were UV-irradiated with doses ranging from 0.1 60 mJ/cm2. Cells counted colony forming assays performed caspase inhibitors.Results In our model HeLa cells, remain >90% viable until 6 hrs after UV radiation (UVR), but more than half dead 12 − 72 UVR. Within dose range between 50 mJ/cm2, viability ranges roughly 20 30%. The difference lowest applied (0.1 mJ/cm2) other is significant, exception next higher 1 activation caspases precedes induction by several hrs. Caspase-9 starts activated at hr UVR followed 3, 7 which fully active 2 while caspase-8 only 3 Most weakly or not mJ/cm2 hrs, same time point increased doses. PARP-1, substrate, cleaved immediately caspases. Colony formation activity tumor decreases exponentially dropping down < 0.01% plating efficiency Interestingly, this drop cannot rescued any two inhibitors tested.Conclusions involves apoptosis-related caspases, seems dispensable for execution Further experiments should clarify mechanisms really necessary type