Acevaltrate promotes apoptosis and inhibits proliferation by suppressing HIF-1α accumulation in cancer cells
Copyright © 2024 Elsevier B.V. All rights reserved..
Acevaltrate is a natural product isolated from the roots of Valeriana glechomifolia F.G.Mey. (Valerianaceae) and has been shown to exhibit anti-cancer activity. However, the mechanism by which acevaltrate inhibits tumor growth is not fully understood. We here demonstrated the effect of acevaltrate on hypoxia-inducible factor-1α (HIF-1α) expression. Acevaltrate showed a potent inhibitory activity against HIF-1α induced by hypoxia in various cancer cells. This compound markedly decreased the hypoxia-induced accumulation of HIF-1α protein dose-dependently. Further analysis revealed that acevaltrate inhibited HIF-1α protein synthesis and promoted degradation of HIF-1α protein, without affecting the expression level of HIF-1α mRNA. Moreover, the phosphorylation levels of mammalian target of rapamycin (mTOR), ribosomal protein S6 kinase (p70S6K), and eIF4E binding protein-1 (4E-BP1) were significantly suppressed by acevaltrate. In addition, acevaltrate promoted apoptosis and inhibited proliferation, which was potentially mediated by suppression of HIF-1α. We also found that acevaltrate administration inhibited tumor growth in mouse xenograft model. Taken together, these results suggested that acevaltrate was a potent inhibitor of HIF-1α and provided a new insight into the mechanisms of acevaltrate against cancers.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:133 |
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| Enthalten in: |
International immunopharmacology - 133(2024) vom: 12. Apr., Seite 112066 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Mi, Chunliu [VerfasserIn] |
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| Links: |
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| Themen: |
Acevaltrate |
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| Anmerkungen: |
Date Revised 14.04.2024 published: Print-Electronic Citation Status Publisher |
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| doi: |
10.1016/j.intimp.2024.112066 |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM371046963 |
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| 520 | |a Acevaltrate is a natural product isolated from the roots of Valeriana glechomifolia F.G.Mey. (Valerianaceae) and has been shown to exhibit anti-cancer activity. However, the mechanism by which acevaltrate inhibits tumor growth is not fully understood. We here demonstrated the effect of acevaltrate on hypoxia-inducible factor-1α (HIF-1α) expression. Acevaltrate showed a potent inhibitory activity against HIF-1α induced by hypoxia in various cancer cells. This compound markedly decreased the hypoxia-induced accumulation of HIF-1α protein dose-dependently. Further analysis revealed that acevaltrate inhibited HIF-1α protein synthesis and promoted degradation of HIF-1α protein, without affecting the expression level of HIF-1α mRNA. Moreover, the phosphorylation levels of mammalian target of rapamycin (mTOR), ribosomal protein S6 kinase (p70S6K), and eIF4E binding protein-1 (4E-BP1) were significantly suppressed by acevaltrate. In addition, acevaltrate promoted apoptosis and inhibited proliferation, which was potentially mediated by suppression of HIF-1α. We also found that acevaltrate administration inhibited tumor growth in mouse xenograft model. Taken together, these results suggested that acevaltrate was a potent inhibitor of HIF-1α and provided a new insight into the mechanisms of acevaltrate against cancers | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Acevaltrate | |
| 650 | 4 | |a Apoptosis | |
| 650 | 4 | |a Cancer | |
| 650 | 4 | |a HIF-1α | |
| 650 | 4 | |a Proliferation | |
| 700 | 1 | |a Zhang, Qiu-Li |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, Meng-Jun |e verfasserin |4 aut | |
| 700 | 1 | |a Lv, You |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, Qiu-Li |e verfasserin |4 aut | |
| 700 | 1 | |a Geng, Shao-Lei |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Tian-Yun |e verfasserin |4 aut | |
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