Meichen Wang, Leilei Liang, Rong Wang, Shutao Jia, Chang Xu, Yuting Wang, Min Luo, Qiqi Lin, Min Yang, Hongyu Zhou, Dandan Liu, Chen Qing
{"title":"水仙素是一种新型的拓扑异构酶I抑制剂，具有很强的抗癌活性。","authors":"Meichen Wang, Leilei Liang, Rong Wang, Shutao Jia, Chang Xu, Yuting Wang, Min Luo, Qiqi Lin, Min Yang, Hongyu Zhou, Dandan Liu, Chen Qing","doi":"10.1007/s13659-023-00392-1","DOIUrl":null,"url":null,"abstract":"<div><p>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<sub>2</sub>/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.</p><h3>Graphical abstract</h3>\n<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":718,"journal":{"name":"Natural Products and Bioprospecting","volume":"13 1","pages":""},"PeriodicalIF":4.8000,"publicationDate":"2023-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10462586/pdf/","citationCount":"0","resultStr":"{\"title\":\"Narciclasine, a novel topoisomerase I inhibitor, exhibited potent anti-cancer activity against cancer cells\",\"authors\":\"Meichen Wang, Leilei Liang, Rong Wang, Shutao Jia, Chang Xu, Yuting Wang, Min Luo, Qiqi Lin, Min Yang, Hongyu Zhou, Dandan Liu, Chen Qing\",\"doi\":\"10.1007/s13659-023-00392-1\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>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<sub>2</sub>/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.</p><h3>Graphical abstract</h3>\\n<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>\",\"PeriodicalId\":718,\"journal\":{\"name\":\"Natural Products and Bioprospecting\",\"volume\":\"13 1\",\"pages\":\"\"},\"PeriodicalIF\":4.8000,\"publicationDate\":\"2023-08-29\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10462586/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Natural Products and Bioprospecting\",\"FirstCategoryId\":\"92\",\"ListUrlMain\":\"https://link.springer.com/article/10.1007/s13659-023-00392-1\",\"RegionNum\":3,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, MEDICINAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Natural Products and Bioprospecting","FirstCategoryId":"92","ListUrlMain":"https://link.springer.com/article/10.1007/s13659-023-00392-1","RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
Narciclasine, a novel topoisomerase I inhibitor, exhibited potent anti-cancer activity against cancer cells
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 G2/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.
期刊介绍：
Natural Products and Bioprospecting serves as an international forum for essential research on natural products and focuses on, but is not limited to, the following aspects:
Natural products: isolation and structure elucidation
Natural products: synthesis
Biological evaluation of biologically active natural products
Bioorganic and medicinal chemistry
Biosynthesis and microbiological transformation
Fermentation and plant tissue cultures
Bioprospecting of natural products from natural resources
All research articles published in this journal have undergone rigorous peer review. In addition to original research articles, Natural Products and Bioprospecting publishes reviews and short communications, aiming to rapidly disseminate the research results of timely interest, and comprehensive reviews of emerging topics in all the areas of natural products. It is also an open access journal, which provides free access to its articles to anyone, anywhere.
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