Induction of IFIT1/IFIT3 and inhibition of Bcl-2 orchestrate the treatment of myeloma and leukemia via pyroptosis
Copyright © 2024 Elsevier B.V. All rights reserved..
Induction of pyroptosis is proposed as a promising strategy for the treatment of hematological malignancies, but little is known. In the present study, we find clioquinol (CLQ), an anti-parasitic drug, induces striking myeloma and leukemia cell pyroptosis on a drug screen. RNA sequencing reveals that the interferon-inducible genes IFIT1 and IFIT3 are markedly upregulated and are essential for CLQ-induced GSDME activation and cell pyroptosis. Specifically, IFIT1 and IFIT3 form a complex with BAX and N-GSDME therefore directing N-GSDME translocalization to mitochondria and increasing mitochondrial membrane permeabilization and triggering pyroptosis. Furthermore, venetoclax, an activator of BAX and an inhibitor of Bcl-2, displays strikingly synergistic effects with CLQ against leukemia and myeloma via pyroptosis. This study thus reveals a novel mechanism for mitochondrial GSDME in pyroptosis and it also illustrates that induction of IFIT1/T3 and inhibition of Bcl-2 orchestrate the treatment of leukemia and myeloma via pyroptosis.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:588 |
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| Enthalten in: |
Cancer letters - 588(2024) vom: 28. Apr., Seite 216797 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
He, Yuanming [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 09.04.2024 Date Revised 09.04.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.canlet.2024.216797 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 245 | 1 | 0 | |a Induction of IFIT1/IFIT3 and inhibition of Bcl-2 orchestrate the treatment of myeloma and leukemia via pyroptosis |
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| 520 | |a Copyright © 2024 Elsevier B.V. All rights reserved. | ||
| 520 | |a Induction of pyroptosis is proposed as a promising strategy for the treatment of hematological malignancies, but little is known. In the present study, we find clioquinol (CLQ), an anti-parasitic drug, induces striking myeloma and leukemia cell pyroptosis on a drug screen. RNA sequencing reveals that the interferon-inducible genes IFIT1 and IFIT3 are markedly upregulated and are essential for CLQ-induced GSDME activation and cell pyroptosis. Specifically, IFIT1 and IFIT3 form a complex with BAX and N-GSDME therefore directing N-GSDME translocalization to mitochondria and increasing mitochondrial membrane permeabilization and triggering pyroptosis. Furthermore, venetoclax, an activator of BAX and an inhibitor of Bcl-2, displays strikingly synergistic effects with CLQ against leukemia and myeloma via pyroptosis. This study thus reveals a novel mechanism for mitochondrial GSDME in pyroptosis and it also illustrates that induction of IFIT1/T3 and inhibition of Bcl-2 orchestrate the treatment of leukemia and myeloma via pyroptosis | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Bcl-2 | |
| 650 | 4 | |a Clioquinol | |
| 650 | 4 | |a Gasdermin E | |
| 650 | 4 | |a Interferon-inducible genes | |
| 650 | 4 | |a Mitochondria | |
| 650 | 4 | |a Pyroptosis | |
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| 650 | 7 | |a Intracellular Signaling Peptides and Proteins |2 NLM | |
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| 650 | 7 | |a Adaptor Proteins, Signal Transducing |2 NLM | |
| 700 | 1 | |a Jiang, Shuoyi |e verfasserin |4 aut | |
| 700 | 1 | |a Cui, Yaoli |e verfasserin |4 aut | |
| 700 | 1 | |a Liang, Jingpei |e verfasserin |4 aut | |
| 700 | 1 | |a Zhong, Yueya |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, Yuening |e verfasserin |4 aut | |
| 700 | 1 | |a Moran, Michael F |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Zhenqian |e verfasserin |4 aut | |
| 700 | 1 | |a He, Guisong |e verfasserin |4 aut | |
| 700 | 1 | |a Mao, Xinliang |e verfasserin |4 aut | |
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