Targeting Histone Acetyltransferase Activity of P300/CBP Domains Impairs Cell Viability and Promotes Senescence in Ewing Sarcoma
The oncogenic activity of Ewing Sarcoma (EWS), an aggressive pediatric osteosarcoma, is promoted by the histone acetyltransferases E1A-binding protein P300 and cyclic AMP response element-binding protein (CBP). In this project, P300/CBP inhibitors were utilized to restrict this interaction as a potential therapeutic approach. SK-ES-1 and TC-71, two EWS cell lines, were used to examine the effect of these inhibitors. The specificity of the P300/CBP inhibitors and their effect on cell viability was evaluated via an ATP assay comparing EWS to HCT-116, a colorectal cancer cell line. Proliferative capacity was assessed by staining for Ki-67 of EWS cells treated with P300/CBP inhibitors, and further analyzed by RT-qPCR for CCND1 and CDK2. Senescence was analyzed by staining for beta-galactosidase, and supported by RT-qPCR for lamin B1 and P15. This study illustrates a promising therapeutic approach utilizing P300/CBP inhibitors.