Narciclasine, a novel topoisomerase I inhibitor, exhibited potent anti-cancer activity against cancer cells
© 2023. Kunming Institute of Botany, CAS..
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.
Medienart: |
E-Artikel |
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Erscheinungsjahr: |
2023 |
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Erschienen: |
2023 |
Enthalten in: |
Zur Gesamtaufnahme - volume:13 |
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Enthalten in: |
Natural products and bioprospecting - 13(2023), 1 vom: 29. Aug., Seite 27 |
Sprache: |
Englisch |
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Beteiligte Personen: |
Wang, Meichen [VerfasserIn] |
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Links: |
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Themen: |
Apoptosis |
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Anmerkungen: |
Date Revised 21.11.2023 published: Electronic Citation Status PubMed-not-MEDLINE |
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doi: |
10.1007/s13659-023-00392-1 |
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funding: |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
NLM361388780 |
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520 | |a 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 | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a Apoptosis | |
650 | 4 | |a Cell cycle | |
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700 | 1 | |a Jia, Shutao |e verfasserin |4 aut | |
700 | 1 | |a Xu, Chang |e verfasserin |4 aut | |
700 | 1 | |a Wang, Yuting |e verfasserin |4 aut | |
700 | 1 | |a Luo, Min |e verfasserin |4 aut | |
700 | 1 | |a Lin, Qiqi |e verfasserin |4 aut | |
700 | 1 | |a Yang, Min |e verfasserin |4 aut | |
700 | 1 | |a Zhou, Hongyu |e verfasserin |4 aut | |
700 | 1 | |a Liu, Dandan |e verfasserin |4 aut | |
700 | 1 | |a Qing, Chen |e verfasserin |4 aut | |
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