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

Autor: Meichen Wang, Leilei Liang, Rong Wang, Shutao Jia, Chang Xu, Yuting Wang, Min Luo, Qiqi Lin, Min Yang, Hongyu Zhou, Dandan Liu, Chen Qing
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Natural Products and Bioprospecting, Vol 13, Iss 1, Pp 1-11 (2023)
Druh dokumentu: article
ISSN: 2192-2195
2192-2209
DOI: 10.1007/s13659-023-00392-1
Popis: Abstract 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. Graphical abstract
Databáze: Directory of Open Access Journals
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