Pyridoxine induces monocyte-macrophages death as specific treatment of acute myeloid leukemia
Copyright © 2020 Elsevier B.V. All rights reserved..
Acute myeloid leukemia (AML) is an aggressive hematological malignancy that gradually develops resistance to current chemotherapy treatments. The available chemotherapy drugs show serious non-specific cytotoxicity to healthy normal cells, resulting in relapse and low survival rates. Natural small molecules with less toxicity and high selectivity for AML are urgently needed. In this study, we confirmed that pyridoxine (vitamin B6) selectively induces monocyte macrophages to undergo programmed cell death in two different modes: caspase-3-dependent apoptosis in U937 cells or GSDME-mediated pyroptosis in THP-1 cells. Further molecular analysis indicated that blocking the caspase pathway could switch the death to MLKL-dependent necroptosis and subsequent extensive inflammatory response. Pyridoxine also delayed the disease progression in a THP-1 leukemia mouse model. In addition, it induced the death of primary AML cells from AML patients by activating caspase-8/3. Overall, our results identify pyridoxine, a low-toxicity natural small molecule, as a potential therapeutic drug for AML treatment.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:492 |
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| Enthalten in: |
Cancer letters - 492(2020) vom: 01. Nov., Seite 96-105 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Yang, Wei [VerfasserIn] |
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| Links: |
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| Themen: |
AML |
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| Anmerkungen: |
Date Completed 19.02.2021 Date Revised 19.02.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.canlet.2020.08.018 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM314339965 |
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| 520 | |a Copyright © 2020 Elsevier B.V. All rights reserved. | ||
| 520 | |a Acute myeloid leukemia (AML) is an aggressive hematological malignancy that gradually develops resistance to current chemotherapy treatments. The available chemotherapy drugs show serious non-specific cytotoxicity to healthy normal cells, resulting in relapse and low survival rates. Natural small molecules with less toxicity and high selectivity for AML are urgently needed. In this study, we confirmed that pyridoxine (vitamin B6) selectively induces monocyte macrophages to undergo programmed cell death in two different modes: caspase-3-dependent apoptosis in U937 cells or GSDME-mediated pyroptosis in THP-1 cells. Further molecular analysis indicated that blocking the caspase pathway could switch the death to MLKL-dependent necroptosis and subsequent extensive inflammatory response. Pyridoxine also delayed the disease progression in a THP-1 leukemia mouse model. In addition, it induced the death of primary AML cells from AML patients by activating caspase-8/3. Overall, our results identify pyridoxine, a low-toxicity natural small molecule, as a potential therapeutic drug for AML treatment | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a AML | |
| 650 | 4 | |a Apoptosis | |
| 650 | 4 | |a Monocytes | |
| 650 | 4 | |a Pyroptosis | |
| 650 | 4 | |a Vitamin B6 | |
| 650 | 7 | |a Oligopeptides |2 NLM | |
| 650 | 7 | |a benzyloxycarbonyl-valyl-alanyl-aspartic acid |2 NLM | |
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| 700 | 1 | |a Liu, Shuai |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Yunlei |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Yujie |e verfasserin |4 aut | |
| 700 | 1 | |a Deng, Yao |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, Weimin |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Hualan |e verfasserin |4 aut | |
| 700 | 1 | |a Xie, Junmou |e verfasserin |4 aut | |
| 700 | 1 | |a He, Andong |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Honglv |e verfasserin |4 aut | |
| 700 | 1 | |a Tao, Ailin |e verfasserin |4 aut | |
| 700 | 1 | |a Yan, Jie |e verfasserin |4 aut | |
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