Regulatory mechanism of α-hederin upon cisplatin sensibility in NSCLC at safe dose by destroying GSS/GSH/GPX2 axis-mediated glutathione oxidation-reduction system
Copyright © 2022. Published by Elsevier Masson SAS..
Emerging studies showed that α-hederin induced autophagic cell death in different cancers via reactive oxygen species. Nevertheless, α-hederin role in non-small-cell lung cancer (NSCLC) remains unknown. So, the aim of this study was to explain whether ferroptosis is a therapeutic strategy to NSCLC, and to explore the effect of α-hederin on NSCLC ferroptosis. Current investigation found that α-hederin inhibited NSCLC cell proliferation, invasion, and migration in vitro and in vivo at toxic doses. The α-hederin treatment also increased NSCLC cell chemosensitivity to cisplatin and promoted ferroptosis and apoptosis at a safe dose. Proteomics, metabolomics, and high-throughput sequencing detection confirmed that α-hederin treatment downregulated glutathione peroxidase 2 (GPX2), and glutathione synthase (GSS) expression suppressed the synthesis of glutathione (GSH), which destroyed the GSH redox system. Eventually, it led to ferroptosis, apoptosis, and membrane permeabilization in NSCLC. Taken together, the study provided molecular data to confirm that α-hederin induced ferroptosis, apoptosis, and membrane permeabilization in NSCLC by destroying the GSS/GSH/GPX2 axis-mediated GSH oxidation-reduction system at a safe and low-toxicity dose.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:150 |
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| Enthalten in: |
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie - 150(2022) vom: 01. Juni, Seite 112927 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Wu, Yue [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 03.06.2022 Date Revised 03.06.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.biopha.2022.112927 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a Emerging studies showed that α-hederin induced autophagic cell death in different cancers via reactive oxygen species. Nevertheless, α-hederin role in non-small-cell lung cancer (NSCLC) remains unknown. So, the aim of this study was to explain whether ferroptosis is a therapeutic strategy to NSCLC, and to explore the effect of α-hederin on NSCLC ferroptosis. Current investigation found that α-hederin inhibited NSCLC cell proliferation, invasion, and migration in vitro and in vivo at toxic doses. The α-hederin treatment also increased NSCLC cell chemosensitivity to cisplatin and promoted ferroptosis and apoptosis at a safe dose. Proteomics, metabolomics, and high-throughput sequencing detection confirmed that α-hederin treatment downregulated glutathione peroxidase 2 (GPX2), and glutathione synthase (GSS) expression suppressed the synthesis of glutathione (GSH), which destroyed the GSH redox system. Eventually, it led to ferroptosis, apoptosis, and membrane permeabilization in NSCLC. Taken together, the study provided molecular data to confirm that α-hederin induced ferroptosis, apoptosis, and membrane permeabilization in NSCLC by destroying the GSS/GSH/GPX2 axis-mediated GSH oxidation-reduction system at a safe and low-toxicity dose | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a Ferroptosis | |
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| 650 | 4 | |a NSCLC | |
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| 700 | 1 | |a Lou, Yuqing |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Xiyu |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Pinzheng |e verfasserin |4 aut | |
| 700 | 1 | |a Jin, Mingming |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Gang |e verfasserin |4 aut | |
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