Cited by 320Sulfur Compounds in BiologyRedox biology and oxidative stressCell death mechanisms and regulation

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Unraveling the Potential Role of Glutathione in Multiple Forms of Cell Death in Cancer Therapy

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Lv, Huanhuan, Zhen, Chenxiao, Liu, Junyu, Yang, Pengfei, Hu, Lijiang, Shang, Peng·2019·Oxidative Medicine and Cellular Longevity

DOI 10.1155/2019/3150145PMC PMC6590529

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Abstract

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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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
ORCID: Lv, Huanhuan
Yang, Pengfei
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
DOI: 10.1155/2019/3150145
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
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (unspecified)
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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Unraveling the Potential Role of Glutathione in Multiple Forms of Cell Death in Cancer Therapy

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