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 $ 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. Graphical abstract.
Medienart: |
E-Artikel |
---|
Erscheinungsjahr: |
2023 |
---|---|
Erschienen: |
2023 |
Enthalten in: |
Zur Gesamtaufnahme - volume:13 |
---|---|
Enthalten in: |
Natural products and bioprospecting - 13(2023), 1 vom: 29. Aug. |
Sprache: |
Englisch |
---|
Beteiligte Personen: |
Wang, Meichen [VerfasserIn] |
---|
Links: |
Volltext [kostenfrei] |
---|
Themen: |
Apoptosis |
---|
Anmerkungen: |
© The Author(s) 2023 |
---|
doi: |
10.1007/s13659-023-00392-1 |
---|
funding: |
|
---|---|
Förderinstitution / Projekttitel: |
|
PPN (Katalog-ID): |
SPR052902315 |
---|
LEADER | 01000caa a22002652 4500 | ||
---|---|---|---|
001 | SPR052902315 | ||
003 | DE-627 | ||
005 | 20231119064908.0 | ||
007 | cr uuu---uuuuu | ||
008 | 230829s2023 xx |||||o 00| ||eng c | ||
024 | 7 | |a 10.1007/s13659-023-00392-1 |2 doi | |
035 | |a (DE-627)SPR052902315 | ||
035 | |a (SPR)s13659-023-00392-1-e | ||
040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
041 | |a eng | ||
100 | 1 | |a Wang, Meichen |e verfasserin |4 aut | |
245 | 1 | 0 | |a Narciclasine, a novel topoisomerase I inhibitor, exhibited potent anti-cancer activity against cancer cells |
264 | 1 | |c 2023 | |
336 | |a Text |b txt |2 rdacontent | ||
337 | |a Computermedien |b c |2 rdamedia | ||
338 | |a Online-Ressource |b cr |2 rdacarrier | ||
500 | |a © The Author(s) 2023 | ||
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 $ 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. Graphical abstract | ||
650 | 4 | |a Topoisomerase |7 (dpeaa)DE-He213 | |
650 | 4 | |a Narciclasine (NCS) |7 (dpeaa)DE-He213 | |
650 | 4 | |a Topo I-DNA covalent complex |7 (dpeaa)DE-He213 | |
650 | 4 | |a DNA damage |7 (dpeaa)DE-He213 | |
650 | 4 | |a Cell cycle |7 (dpeaa)DE-He213 | |
650 | 4 | |a Apoptosis |7 (dpeaa)DE-He213 | |
700 | 1 | |a Liang, Leilei |4 aut | |
700 | 1 | |a Wang, Rong |4 aut | |
700 | 1 | |a Jia, Shutao |4 aut | |
700 | 1 | |a Xu, Chang |4 aut | |
700 | 1 | |a Wang, Yuting |4 aut | |
700 | 1 | |a Luo, Min |4 aut | |
700 | 1 | |a Lin, Qiqi |4 aut | |
700 | 1 | |a Yang, Min |4 aut | |
700 | 1 | |a Zhou, Hongyu |0 (orcid)0000-0001-5852-3953 |4 aut | |
700 | 1 | |a Liu, Dandan |4 aut | |
700 | 1 | |a Qing, Chen |4 aut | |
773 | 0 | 8 | |i Enthalten in |t Natural products and bioprospecting |d Heidelberg : Springer, 2011 |g 13(2023), 1 vom: 29. Aug. |w (DE-627)SPR032198485 |w (DE-600)2636293-4 |x 2192-2209 |7 nnns |
773 | 1 | 8 | |g volume:13 |g year:2023 |g number:1 |g day:29 |g month:08 |
856 | 4 | 0 | |u https://dx.doi.org/10.1007/s13659-023-00392-1 |z kostenfrei |3 Volltext |
912 | |a GBV_USEFLAG_A | ||
912 | |a GBV_SPRINGER | ||
951 | |a AR | ||
952 | |d 13 |j 2023 |e 1 |b 29 |c 08 |