The Cold Atmospheric Plasma Inhibits Cancer Proliferation Through Reducing Glutathione Synthesis

(1) Objective: Cold atmospheric plasma (CAP) is a safe and effective alternative to radiotherapy for cancer treatment. Its anticancer effects are attributed to increased intracellular reactive oxygen species (ROS). Glutathione, a key antioxidant derived from glutamine, is critical for cell prolifera...

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Main Authors: Qiyu Yang, Wei Zhao, Lingling Yang, Yongqin Fan, Changsheng Shao, Tao Wang, Fengqiu Zhang
Format: Article
Language:English
Published: MDPI AG 2025-06-01
Series:Molecules
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Online Access:https://www.mdpi.com/1420-3049/30/13/2808
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author Qiyu Yang
Wei Zhao
Lingling Yang
Yongqin Fan
Changsheng Shao
Tao Wang
Fengqiu Zhang
author_facet Qiyu Yang
Wei Zhao
Lingling Yang
Yongqin Fan
Changsheng Shao
Tao Wang
Fengqiu Zhang
author_sort Qiyu Yang
collection DOAJ
description (1) Objective: Cold atmospheric plasma (CAP) is a safe and effective alternative to radiotherapy for cancer treatment. Its anticancer effects are attributed to increased intracellular reactive oxygen species (ROS). Glutathione, a key antioxidant derived from glutamine, is critical for cell proliferation. This study investigated whether CAP-induced ROS elevation results from reduced glutamine–glutathione conversion and elucidates the underlying mechanisms. (2) Methods: Using esophageal squamous carcinoma cell models (Ec9706 and Eca109), we analyzed CAP’s effects on key enzymes in glutamine metabolism (Glutaminase 1 and γ-glutamylcysteine ligase) and proliferation-related genes (e.g., Retinoblastoma and Nuclear respiratory factor 2). Transcriptome analysis further explored molecular pathways involved in CAP-mediated anticancer effects. (3) Results: CAP reduced Glutaminase 1 and γ-glutamylcysteine ligase expression, leading to lower intracellular glutathione, higher ROS activity, and enhanced apoptosis. Transcriptome data confirmed CAP’s role in oxidation-reduction reactions and glutamine metabolism. (4) Conclusions: This study provides the first mechanistic insights into CAP’s anticancer effects by targeting glutamine metabolism. While based on in vitro assays, these findings guide the development of novel CAP therapies for currently incurable cancers.
format Article
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institution Kabale University
issn 1420-3049
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publishDate 2025-06-01
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series Molecules
spelling doaj-art-ea17fcc2338143f1b752dadd4de773052025-08-20T03:49:55ZengMDPI AGMolecules1420-30492025-06-013013280810.3390/molecules30132808The Cold Atmospheric Plasma Inhibits Cancer Proliferation Through Reducing Glutathione SynthesisQiyu Yang0Wei Zhao1Lingling Yang2Yongqin Fan3Changsheng Shao4Tao Wang5Fengqiu Zhang6School of Physics and Laboratory of Zhongyuan Light, Zhengzhou University, Zhengzhou 450001, ChinaSchool of Physics and Laboratory of Zhongyuan Light, Zhengzhou University, Zhengzhou 450001, ChinaHenan Key Laboratory of Ion-Beam Green Agriculture Bioengineering, Zhengzhou University, Zhengzhou 450001, ChinaHenan Key Laboratory of Ion-Beam Green Agriculture Bioengineering, Zhengzhou University, Zhengzhou 450001, ChinaCAS Key Laboratory of High Magnetic Field and Ion Beam Physical Biology, Hefei Institutes of Physical Sciences, Chinese Academy of Sciences, Hefei 230031, ChinaCollege of Nursing and Health, Zhengzhou University, Zhengzhou 450001, ChinaSchool of Physics and Laboratory of Zhongyuan Light, Zhengzhou University, Zhengzhou 450001, China(1) Objective: Cold atmospheric plasma (CAP) is a safe and effective alternative to radiotherapy for cancer treatment. Its anticancer effects are attributed to increased intracellular reactive oxygen species (ROS). Glutathione, a key antioxidant derived from glutamine, is critical for cell proliferation. This study investigated whether CAP-induced ROS elevation results from reduced glutamine–glutathione conversion and elucidates the underlying mechanisms. (2) Methods: Using esophageal squamous carcinoma cell models (Ec9706 and Eca109), we analyzed CAP’s effects on key enzymes in glutamine metabolism (Glutaminase 1 and γ-glutamylcysteine ligase) and proliferation-related genes (e.g., Retinoblastoma and Nuclear respiratory factor 2). Transcriptome analysis further explored molecular pathways involved in CAP-mediated anticancer effects. (3) Results: CAP reduced Glutaminase 1 and γ-glutamylcysteine ligase expression, leading to lower intracellular glutathione, higher ROS activity, and enhanced apoptosis. Transcriptome data confirmed CAP’s role in oxidation-reduction reactions and glutamine metabolism. (4) Conclusions: This study provides the first mechanistic insights into CAP’s anticancer effects by targeting glutamine metabolism. While based on in vitro assays, these findings guide the development of novel CAP therapies for currently incurable cancers.https://www.mdpi.com/1420-3049/30/13/2808cancercold atmospheric plasmaesophageal squamous carcinomaglutamine metabolismglutathione
spellingShingle Qiyu Yang
Wei Zhao
Lingling Yang
Yongqin Fan
Changsheng Shao
Tao Wang
Fengqiu Zhang
The Cold Atmospheric Plasma Inhibits Cancer Proliferation Through Reducing Glutathione Synthesis
Molecules
cancer
cold atmospheric plasma
esophageal squamous carcinoma
glutamine metabolism
glutathione
title The Cold Atmospheric Plasma Inhibits Cancer Proliferation Through Reducing Glutathione Synthesis
title_full The Cold Atmospheric Plasma Inhibits Cancer Proliferation Through Reducing Glutathione Synthesis
title_fullStr The Cold Atmospheric Plasma Inhibits Cancer Proliferation Through Reducing Glutathione Synthesis
title_full_unstemmed The Cold Atmospheric Plasma Inhibits Cancer Proliferation Through Reducing Glutathione Synthesis
title_short The Cold Atmospheric Plasma Inhibits Cancer Proliferation Through Reducing Glutathione Synthesis
title_sort cold atmospheric plasma inhibits cancer proliferation through reducing glutathione synthesis
topic cancer
cold atmospheric plasma
esophageal squamous carcinoma
glutamine metabolism
glutathione
url https://www.mdpi.com/1420-3049/30/13/2808
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