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

Author:

Lv Huanhuan12345ORCID,Zhen Chenxiao125,Liu Junyu125,Yang Pengfei1245,Hu Lijiang3,Shang Peng245ORCID

Affiliation:

1. School of Life Sciences, Northwestern Polytechnical University, Xi’an, Shaanxi 710072, China

2. Research & Development Institute of Northwestern Polytechnical University in Shenzhen, Shenzhen 518057, China

3. Zhejiang Heye Health Technology Co. Ltd., Anji, Zhejiang 313300, China

4. Research Centre of Microfluidic Chip for Health Care and Environmental Monitoring, Yangtze River Delta Research Institute of Northwestern Polytechnical University in Taicang, Suzhou, Jiangsu 215400, China

5. Key Laboratory for Space Bioscience and Biotechnology, Northwestern Polytechnical University, Xi’an, Shaanxi 710072, China

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.

Funder

Northwestern Polytechnical University Foundation for Fundamental Research

Publisher

Hindawi Limited

Subject

Cell Biology,Aging,General Medicine,Biochemistry

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