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Unraveling the Potential Role of Glutathione in Multiple Forms of Cell Death in Cancer Therapy
Open accessAbstract
Glutathione is the principal intracellular antioxidant buffer against oxidative stress and mainly exists in the forms of reduced glutathione (GSH) and oxidized glutathione (GSSG). The processes of glutathione synthesis, transport, utilization, and metabolism are tightly controlled to maintain intracellular glutathione homeostasis and redox balance. As for cancer cells, they exhibit a greater ROS level than normal cells in order to meet the enhanced metabolism and vicious proliferation; meanwhile, they also have to develop an increased antioxidant defense system to cope with the higher oxidant state. Growing numbers of studies have implicated that altering the glutathione antioxidant system is associated with multiple forms of programmed cell death in cancer cells. In this review, we firstly focus on glutathione homeostasis from the perspectives of glutathione synthesis, distribution, transportation, and metabolism. Then, we discuss the function of glutathione in the antioxidant process. Afterwards, we also summarize the recent advance in the understanding of the mechanism by which glutathione plays a key role in multiple forms of programmed cell death, including apoptosis, necroptosis, ferroptosis, and autophagy. Finally, we highlight the glutathione-targeting therapeutic approaches toward cancers. A comprehensive review on the glutathione homeostasis and the role of glutathione depletion in programmed cell death provide insight into the redox-based research concerning cancer therapeutics.
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“Being the main intracellular antioxidant buffer, both the levels of GSH and GSH/GSSH ratio are tightly controlled through a fine regulation of their synthesis, metabolism, transport, and degradation [176,177].”
From The Role of Antioxidants in the Interplay between Oxidative Stress and Senescence (2022) · cites this paper as [177]
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“Glutathione can exist in two forms: reduced glutathione (GSH) and oxidized glutathione (GSSG), which are converted into each other by the enzymatic activity of GPx (that links two GSH in one GSSG through the formation of a disulphide bond) and glutathione reductase (that catalyses the reduction of one GSSG into two GSH to the expenses of NADPH) [177].”
From The Role of Antioxidants in the Interplay between Oxidative Stress and Senescence (2022) · cites this paper as [177]
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Metadata
- Authors
- Lv, H., Zhen, C., Liu, J., Yang, P., Hu, L., & Shang, P.
- Affiliations
- Northwestern Polytechnical University (CN)
- Zhejiang Heye Health Technology Co. Ltd., Anji, Zhejiang 313300, China
- Corresponding author
- Shang, Peng
- Venue
- Oxidative Medicine and Cellular Longevity
- Publisher
- Wiley
- Published
- 2019-06-10
- Volume
- 2019
- Pages
- 1-16
- ISSN
- 1942-0994 (ISSN-L)
- 1942-0900
- PMC
- PMC6590529
- OpenAlex
- W2949432489
- Cited by
- 320
- References
- 164
- Citations by year
- 2026: 15 · 2025: 34 · 2024: 78 · 2023: 64 · 2022: 43 · 2021: 46 · 2020: 35 · 2019: 4
- FWCI
- 3.50
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Oxidative Medicine and Cellular Longevity (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Northwestern Polytechnical University Foundation for Fundamental Research (3102018JGC012, 3102017OQD111, 51777171, 11872316, 81803032)
- Fundamental Research Funds for the Central Universities (3102018JGC012, 3102017OQD111, 51777171, 11872316, 81803032)
- National Natural Science Foundation of China (3102018JGC012, 3102017OQD111, 51777171, 11872316, 81803032)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Sulfur Compounds in Biology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Keywords
- glutathione, glutathione homeostasis, redox homeostasis, oxidative stress, cancer cells, programmed cell death, apoptosis, necroptosis, ferroptosis, autophagy, glutathione depletion, glutathione metabolism
- MeSH terms
- Glutathione, Humans, Neoplasms, Cell Death
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