Decitabine combined with cold atmospheric plasma induces pyroptosis via the ROS/Caspase-3/GSDME signaling pathway in Ovcar5 cells
Copyright © 2023. Published by Elsevier B.V..
BACKGROUND: High methylation of the DFNA5 gene results in the absence of GSDME, a key protein that mediates pyroptosis, while decitabine demethylates the DFNA5 gene, resulting in high expression of the GSDME protein. Cold atmospheric plasma (CAP) is a novel anti-cancer method that induces tumor cell death.
METHODS: The pyroptosis induced by decitabine in combination with CAP in Ovcar5 cells was evaluated. In particular, mitochondrial membrane potential was estimated by JC-1 staining, dehydrogenase (LDH) release was assessed by ELISA, Annexin V/PI staining was detected by flow cytometry, the cell cycle changes were evaluated using PI staining followed by detection by flow cytometry, and Caspase-9 cleavage, Caspase-3 cleavage and GSDME expression were evaluated by western blot.
RESULTS: Decitabine resulted in high expression of the GSDME in Ovcar5 in a concentration-dependent manner and increased tumor cell sensitivity to CAP. CAP induced mitochondrial damage and activated the Caspase-9/Caspase-3 pathway. Therefore, decitabine combined with CAP induced Ovcar5 cell pyroptosis through Caspase-3 mediated GSDME cleavage. Reactive oxygen species (ROS) generated by CAP treatment played an important role in the CAP/decitabine combination-induced production of ROS, activation of Caspase-9/Caspase-3, GSDME cleavage and pyroptosis that ROS scavenger NAC inhibited all these processes.
CONCLUSIONS: CAP combined with decitabine induced Caspase-3 activation, which cleaved decitabine-upregulated GSDME and ediated pyroptosis.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:1868 |
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| Enthalten in: |
Biochimica et biophysica acta. General subjects - 1868(2024), 6 vom: 15. Apr., Seite 130602 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Du, Liang [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 25.04.2024 Date Revised 29.04.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.bbagen.2024.130602 |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM370035054 |
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| 100 | 1 | |a Du, Liang |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Decitabine combined with cold atmospheric plasma induces pyroptosis via the ROS/Caspase-3/GSDME signaling pathway in Ovcar5 cells |
| 264 | 1 | |c 2024 | |
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| 500 | |a Date Completed 25.04.2024 | ||
| 500 | |a Date Revised 29.04.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023. Published by Elsevier B.V. | ||
| 520 | |a BACKGROUND: High methylation of the DFNA5 gene results in the absence of GSDME, a key protein that mediates pyroptosis, while decitabine demethylates the DFNA5 gene, resulting in high expression of the GSDME protein. Cold atmospheric plasma (CAP) is a novel anti-cancer method that induces tumor cell death | ||
| 520 | |a METHODS: The pyroptosis induced by decitabine in combination with CAP in Ovcar5 cells was evaluated. In particular, mitochondrial membrane potential was estimated by JC-1 staining, dehydrogenase (LDH) release was assessed by ELISA, Annexin V/PI staining was detected by flow cytometry, the cell cycle changes were evaluated using PI staining followed by detection by flow cytometry, and Caspase-9 cleavage, Caspase-3 cleavage and GSDME expression were evaluated by western blot | ||
| 520 | |a RESULTS: Decitabine resulted in high expression of the GSDME in Ovcar5 in a concentration-dependent manner and increased tumor cell sensitivity to CAP. CAP induced mitochondrial damage and activated the Caspase-9/Caspase-3 pathway. Therefore, decitabine combined with CAP induced Ovcar5 cell pyroptosis through Caspase-3 mediated GSDME cleavage. Reactive oxygen species (ROS) generated by CAP treatment played an important role in the CAP/decitabine combination-induced production of ROS, activation of Caspase-9/Caspase-3, GSDME cleavage and pyroptosis that ROS scavenger NAC inhibited all these processes | ||
| 520 | |a CONCLUSIONS: CAP combined with decitabine induced Caspase-3 activation, which cleaved decitabine-upregulated GSDME and ediated pyroptosis | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Cold atmospheric plasma | |
| 650 | 4 | |a Decitabine | |
| 650 | 4 | |a Ovcar5 | |
| 650 | 4 | |a Pyroptosis | |
| 650 | 4 | |a ROS | |
| 650 | 7 | |a Decitabine |2 NLM | |
| 650 | 7 | |a 776B62CQ27 |2 NLM | |
| 650 | 7 | |a Reactive Oxygen Species |2 NLM | |
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| 650 | 7 | |a GSDME protein, human |2 NLM | |
| 650 | 7 | |a Plasma Gases |2 NLM | |
| 650 | 7 | |a CASP3 protein, human |2 NLM | |
| 650 | 7 | |a EC 3.4.22.- |2 NLM | |
| 650 | 7 | |a Antimetabolites, Antineoplastic |2 NLM | |
| 650 | 7 | |a Gasdermins |2 NLM | |
| 700 | 1 | |a Ming, Huiyun |e verfasserin |4 aut | |
| 700 | 1 | |a Yan, Zhuna |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Jinwu |e verfasserin |4 aut | |
| 700 | 1 | |a Song, Wencheng |e verfasserin |4 aut | |
| 700 | 1 | |a Dai, Haiming |e verfasserin |4 aut | |
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