Narciclasine,a novel topoisomerase I inhibitor,exhibited potent anti-cancer activity against cancer cells  

作　　者：Meichen Wang Leilei Liang Rong Wang Shutao Jia Chang Xu Yuting Wang Min Luo Qiqi Lin Min Yang Hongyu Zhou Dandan Liu Chen Qing 

机构地区：[1]School of Pharmaceutical Science and Yunnan Key Laboratory of Pharmacology for Natural Products,Kunming Medical University,1168 Western Chunrong Road,Yuhua Street,Cheng Gong District,Kunming 650500,Yunnan,People’s Republic of China [2]Cell Biology and Molecular Biology Laboratory of Experimental Teaching Center,Faculty of Basic Medical Science,Kunming Medical University,1168 Western Chunrong Road,Yuhua Street,Cheng Gong District,Kunming 650500,Yunnan,China [3]Yunnan Infectious Disease Hospital,28 km at Shi’an Road,Taiping Town,Anning,Kunming 650301,Yunnan,China

出　　处：《Natural Products and Bioprospecting》2023年第1期482-492,共11页应用天然产物（英文）

基　　金：the National Natural Science Foundation of China(Grant Nos.21907044,81460559 and 82160697);Yunnan Fundamental Research Projects(Grant Nos.202101AT070155 and 202201AS070086);Basic Research Plan of Yunnan Provincial Science and Technology Department-Kunming Medical University(Grant Nos.202101AY070001-011,202201AY070001-003 and 202101AY070001-041);the Ten Thousand Talent Plans for Young Top-notch Talents of Yunnan Province(Hongyu Zhou,Dandan Liu),Yunnan Academician Expert Workstation(Grant No.202305AF150054);Basic Research Project of Yunnan Provincial Department of Education(Grant No.2022J0213).

摘　　要：DNA topoisomerases are essential nuclear enzymes in correcting topological DNA errors and maintaining DNA integrity.Topoisomerase inhibitors are a significant class of cancer chemotherapeutics with a definite curative effect.Natural products are a rich source of lead compounds for drug discovery,including anti-tumor drugs.In this study,we found that narciclasine(NCS),an amaryllidaceae alkaloid,is a novel inhibitor of topoisomerase I(topo I).Our data demonstrated that NCS inhibited topo I activity and reversed its unwinding effect on p-HOT DNA substrate.However,it had no obvious effect on topo II activity.The molecular mechanism of NCS inhibited topo I showed that NCS did not stabilize topo-DNA covalent complexes in cells,indicating that NCS is not a topo I poison.A blind docking result showed that NCS could bind to topo I,suggesting that NCS might be a topo I suppressor.Additionally,NCS exhibited a potent anti-proliferation effect in various cancer cells.NCS arrested the cell cycle at G_(2)/M phase and induced cell apoptosis.Our study reveals the antitumor mechanisms of NCS and provides a good foundation for the development of anti-cancer drugs based on topo I inhibition.

关 键 词：TOPOISOMERASE Narciclasine(NCS) Topo I-DNA covalent complex DNA damage Cell cycle Apoptosis 

分 类 号：R730[医药卫生—肿瘤]