中国药理学通报2026，Vol.42Issue(10)：1839-1847,9.DOI:10.12360/CPB202512119
华蟾毒精靶向多聚ADP核糖聚合酶1诱导DNA损伤和凋亡
Cinobufagin induces DNA damage and apoptosis by targeting poly(adp-ribose)polymerase 1
摘要
Abstract
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.关键词
华蟾毒精/PARP1/抗肿瘤/多组学技术/DNA损伤修复/细胞凋亡Key words
cinobufagin/PARP1/anti-tumor/multi-omics technologies/DNA damage repair/cell apopto-sis分类
医药卫生引用本文复制引用
游钰卓,柯细松,张雪,周香莲..华蟾毒精靶向多聚ADP核糖聚合酶1诱导DNA损伤和凋亡[J].中国药理学通报,2026,42(10):1839-1847,9.基金项目
国家自然科学基金资助项目(No 82274147). （No 82274147）
