Rapid Screening of Active Components with Topoisomerase I Inhibitory Activity in Sophora alopecuroides L. Based on Ultrafiltration Coupled with UPLC-QTOF-MS
Copyright© Bentham Science Publishers; For any queries, please email at epubbenthamscience.net..
BACKGROUND: Topoisomerase I (Topo I) is a key target of many antitumor drugs in vivo. Alkaloids in Sophora alopecuroides L. can reportedly inhibit Topo I activity, but the pharmacodynamic material basis has not yet been determined.
OBJECTIVE: This study aimed to rapidly identify active components which inhibit Topo I in S. alopecuroides L.
METHODS: Affinity ultrafiltration coupled with ultra-performance liquid chromatography-quadrupole time of flight-mass spectrometry (UF-UPLC-QTOF-MS) screening system based on Topo I protein was established to screen and isolate a total alkaloid fraction in S. alopecuroides L. Topo I inhibitory activity and anti-tumor proliferation activity of the screened components were evaluated, and their molecular mechanisms were studied.
RESULTS: Six compounds that bound specifically to Topo I were obtained. Further screening showed that matrine, cytisine, and sophoridine presented higher inhibitory activity on Topo I and were able to inhibit the proliferation of breast cancer MDA-MB-468 cells with IC50 values of 9.40 ± 1.12 mM, 17.4 ± 2.20 mM, and 10.4 ± 1.37 mM, respectively. To the best of our knowledge, their dual molecular mechanisms against Topo I have not discussed to date. In this study, the following dual mechanisms are reviewed for the first time: (1) stabilization of the Topo I-DNA complex and (2) inhibition or blocking of Topo I binding to DNA.
CONCLUSION: Matrine, cytisine, and sophoridine from S. alopecuroides L. were defined as the active components possessing Topo I inhibitory activity, and their pharmacological mechanism was confirmed, which provided an important base for further research and development of antitumor components from S. alopecuroides L.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:23 |
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| Enthalten in: |
Current pharmaceutical biotechnology - 23(2022), 7 vom: 19., Seite 998-1008 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zhang, Lin [VerfasserIn] |
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| Links: |
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| Themen: |
Active components group |
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| Anmerkungen: |
Date Completed 12.04.2022 Date Revised 12.04.2022 published: Print Citation Status MEDLINE |
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| doi: |
10.2174/1389201022666210602105609 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM326293329 |
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| 245 | 1 | 0 | |a Rapid Screening of Active Components with Topoisomerase I Inhibitory Activity in Sophora alopecuroides L. Based on Ultrafiltration Coupled with UPLC-QTOF-MS |
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| 500 | |a Date Revised 12.04.2022 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright© Bentham Science Publishers; For any queries, please email at epubbenthamscience.net. | ||
| 520 | |a BACKGROUND: Topoisomerase I (Topo I) is a key target of many antitumor drugs in vivo. Alkaloids in Sophora alopecuroides L. can reportedly inhibit Topo I activity, but the pharmacodynamic material basis has not yet been determined | ||
| 520 | |a OBJECTIVE: This study aimed to rapidly identify active components which inhibit Topo I in S. alopecuroides L | ||
| 520 | |a METHODS: Affinity ultrafiltration coupled with ultra-performance liquid chromatography-quadrupole time of flight-mass spectrometry (UF-UPLC-QTOF-MS) screening system based on Topo I protein was established to screen and isolate a total alkaloid fraction in S. alopecuroides L. Topo I inhibitory activity and anti-tumor proliferation activity of the screened components were evaluated, and their molecular mechanisms were studied | ||
| 520 | |a RESULTS: Six compounds that bound specifically to Topo I were obtained. Further screening showed that matrine, cytisine, and sophoridine presented higher inhibitory activity on Topo I and were able to inhibit the proliferation of breast cancer MDA-MB-468 cells with IC50 values of 9.40 ± 1.12 mM, 17.4 ± 2.20 mM, and 10.4 ± 1.37 mM, respectively. To the best of our knowledge, their dual molecular mechanisms against Topo I have not discussed to date. In this study, the following dual mechanisms are reviewed for the first time: (1) stabilization of the Topo I-DNA complex and (2) inhibition or blocking of Topo I binding to DNA | ||
| 520 | |a CONCLUSION: Matrine, cytisine, and sophoridine from S. alopecuroides L. were defined as the active components possessing Topo I inhibitory activity, and their pharmacological mechanism was confirmed, which provided an important base for further research and development of antitumor components from S. alopecuroides L | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Sophora alopecuroides L | |
| 650 | 4 | |a UF-UPLC-QTOF-MS | |
| 650 | 4 | |a active components group | |
| 650 | 4 | |a effective substances | |
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| 700 | 1 | |a Yin, Xiaoying |e verfasserin |4 aut | |
| 700 | 1 | |a Wan, Xi |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, Yun |e verfasserin |4 aut | |
| 700 | 1 | |a Cao, Menghui |e verfasserin |4 aut | |
| 700 | 1 | |a Ouyang, Sheng |e verfasserin |4 aut | |
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