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

Oxidative Medicine and Cellular Longevity - Tập 2019 - Trang 1-16 - 2019
Huanhuan Lv1,2,3,4,5, Chenxiao Zhen1,6,2, Junyu Liu1,6,2, Pengfei Yang1,2,3,4, Lijiang Hu5, Peng Shang1,2,4
1Key Laboratory for Space Bioscience and Biotechnology, Northwestern Polytechnical University, Xi'an, Shaanxi 710072, China
2Research & Development Institute of Northwestern Polytechnical University in Shenzhen, Shenzhen 518057, China
3Research Centre of Microfluidic Chip for Health Care and Environmental Monitoring, Yangtze River Delta Research Institute of Northwestern Polytechnical University in Taicang, Suzhou, Jiangsu 215400
4Research 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
5Zhejiang Heye Health Technology Co., Ltd, Anji, Zhejiang, 313300, China
6Research & Development Institute of Northwestern Polytechnical University in Shenzhen, Shenzhen 518057

Tóm tắt

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.

Từ khóa


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