Revealing active components and action mechanism of Fritillariae Bulbus against non-small cell lung cancer through spectrum-effect relationship and proteomics
Copyright © 2022 Elsevier GmbH. All rights reserved..
BACKGROUND: Fritillariae Bulbus (FB) is widely used as a traditional medicine for the treatment of lung meridian diseases. It has been proved that FB has good anti-non-small cell lung cancer (NSCLC) activity. However, the active components and potential mechanism are still not clear.
PURPOSE: To reveal the bioactive components of FB against NSCLC and potential mechanism through spectrum-effect relationship and proteomics.
METHOD: First, the FB extract was chemically profiled by UHPLC-QTOF-MS and the inhibitory effect of FB extract on A549 cell viability was evaluated by Cell Counting Kit-8 assay. Second, orthogonal-partial least squares-regression analysis was applied to screen potential active compounds through correlating the chemical profile with corresponding inhibitory effect. Third, the anti-NSCLC activities of potential active components were further investigated in terms of cell proliferation, cell cycle and cell apoptosis in vitro and tumor growth in vivo. Finally, proteomics was utilized to reveal the underlying anti-NSCLC mechanism.
RESULTS: Six potential active components including verticine, verticinone, zhebeirine, ebeiedinone, yibeissine and peimisine were screened out by spectrum-effect relationship. Among them, zhebeirine showed higher inhibitory effect on A549 cell viability with IC50 value of 36.93 μM and dosage-dependent inhibition of A549 xenograft tumor growth in nude mice. Proteomics and western blotting assays indicated that zhebeirine could arrest cell cycle by down-regulating the expressions of CDK1, CDK2, Cyclin A2, Cyclin B2 and inhibiting the phosphorylation of p53. Moreover, the proteins participating in p53 signaling pathway including PCNA, 14-3-3σ, CHEK1 were significantly decreased, which suggested that zhebeirine affected cell cycle progression through p53 signaling pathway.
CONCLUSION: This study not only provides scientific evidence to support the clinical application of FB against NSCLC, but also demonstrates that zhebeirine is a promising anti-NSCLC lead compound deserving further studies.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:110 |
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| Enthalten in: |
Phytomedicine : international journal of phytotherapy and phytopharmacology - 110(2023) vom: 15. Feb., Seite 154635 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Liu, Feng-Jie [VerfasserIn] |
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| Links: |
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| Themen: |
Fritillariae Bulbus |
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| Anmerkungen: |
Date Completed 24.01.2023 Date Revised 01.02.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.phymed.2022.154635 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM350987343 |
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| 100 | 1 | |a Liu, Feng-Jie |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Revealing active components and action mechanism of Fritillariae Bulbus against non-small cell lung cancer through spectrum-effect relationship and proteomics |
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| 500 | |a Date Revised 01.02.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2022 Elsevier GmbH. All rights reserved. | ||
| 520 | |a BACKGROUND: Fritillariae Bulbus (FB) is widely used as a traditional medicine for the treatment of lung meridian diseases. It has been proved that FB has good anti-non-small cell lung cancer (NSCLC) activity. However, the active components and potential mechanism are still not clear | ||
| 520 | |a PURPOSE: To reveal the bioactive components of FB against NSCLC and potential mechanism through spectrum-effect relationship and proteomics | ||
| 520 | |a METHOD: First, the FB extract was chemically profiled by UHPLC-QTOF-MS and the inhibitory effect of FB extract on A549 cell viability was evaluated by Cell Counting Kit-8 assay. Second, orthogonal-partial least squares-regression analysis was applied to screen potential active compounds through correlating the chemical profile with corresponding inhibitory effect. Third, the anti-NSCLC activities of potential active components were further investigated in terms of cell proliferation, cell cycle and cell apoptosis in vitro and tumor growth in vivo. Finally, proteomics was utilized to reveal the underlying anti-NSCLC mechanism | ||
| 520 | |a RESULTS: Six potential active components including verticine, verticinone, zhebeirine, ebeiedinone, yibeissine and peimisine were screened out by spectrum-effect relationship. Among them, zhebeirine showed higher inhibitory effect on A549 cell viability with IC50 value of 36.93 μM and dosage-dependent inhibition of A549 xenograft tumor growth in nude mice. Proteomics and western blotting assays indicated that zhebeirine could arrest cell cycle by down-regulating the expressions of CDK1, CDK2, Cyclin A2, Cyclin B2 and inhibiting the phosphorylation of p53. Moreover, the proteins participating in p53 signaling pathway including PCNA, 14-3-3σ, CHEK1 were significantly decreased, which suggested that zhebeirine affected cell cycle progression through p53 signaling pathway | ||
| 520 | |a CONCLUSION: This study not only provides scientific evidence to support the clinical application of FB against NSCLC, but also demonstrates that zhebeirine is a promising anti-NSCLC lead compound deserving further studies | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Fritillariae Bulbus | |
| 650 | 4 | |a Non-small cell lung cancer | |
| 650 | 4 | |a Spectrum-effect relationship | |
| 650 | 4 | |a Steroidal alkaloid | |
| 650 | 4 | |a proteomics | |
| 650 | 7 | |a Tumor Suppressor Protein p53 |2 NLM | |
| 700 | 1 | |a Chen, Xu-Yan |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Jiao |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Zhen |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Qiao-Lei |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Ping |e verfasserin |4 aut | |
| 700 | 1 | |a Jiang, Yan |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Hui-Jun |e verfasserin |4 aut | |
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