华蟾毒精靶向多聚ADP核糖聚合酶1诱导DNA损伤和凋亡OA

Aim To investigate the anti-tumor mecha-nism of Cinobufagin(CBG)by integrating multi-omics analysis,and explore how CBG induces DNA damage and promotes tumor cell apoptosis by targeting poly(ADP-ribose)polymerase-1(PARP1).Methods An integrated multi-omics approach combining transcrip-tomics and proteomics,coupled with Drug Affinity Re-sponsive Target Stability-Mass Spectrometry(DARTS-MS),was employed to identify the potential target PARP1 of CBG.Subsequent enzymatic assays,West-ern blot,and immunofluorescence were conducted to evaluate the impact of CBG on PARP1 function and downstream signaling.Results Multi-omics and DARTS-MS analyses identified PARP1 as a potential target of CBG.After CBG treatment,PARP1 enzymatic activity was significantly inhibited,thereby promot-ing"PARP trapping"at DNA damage sites,which in turn led to the accumulation of DNA damage(elevatedγH2AX)and cascade activation of the caspase-8/3,ulti-mately inducing apoptosis.Notably,PARP1 knock-down significantly reversed the above effects,indicat-ing that PARP1 played a key role in the anti-tumor ef-fect of CBG.Conclusions This study characterizes PARP1 as a functional target of CBG and reveals that CBG exerts anti-tumor effects by inhibiting PARP1-me-diated DNA repair and inducing apoptosis,providing a novel theoretical basis for the anti-tumor research of CBG.