Thioredoxin and Glutathione Systems: Cancer Cells’ Defensive Weapons Against Oxidative Stress
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Author(s)
Yu, Yezhou
Di Trapani, Giovanna
Tonissen, Kathryn
Year published
2021
Metadata
Show full item recordAbstract
Most cancer cells contain high levels of reactive oxygen species (ROS), which result in higher expression levels of the glutathione and thioredoxin reductase systems. These antioxidant systems convert ROS to non-harmful compounds and they also reduce disulphide bonds in oxidised proteins. They also control the glutathionylation and nitrosylation of proteins, which alters the activity of the proteins. Through these functions the upregulated antioxidant systems act on transcription factors and on signalling pathways, which results in the promotion of cancer cell growth and the prevention of cell apoptosis. High levels of ...
View more >Most cancer cells contain high levels of reactive oxygen species (ROS), which result in higher expression levels of the glutathione and thioredoxin reductase systems. These antioxidant systems convert ROS to non-harmful compounds and they also reduce disulphide bonds in oxidised proteins. They also control the glutathionylation and nitrosylation of proteins, which alters the activity of the proteins. Through these functions the upregulated antioxidant systems act on transcription factors and on signalling pathways, which results in the promotion of cancer cell growth and the prevention of cell apoptosis. High levels of certain members of the glutathione and thioredoxin systems in specific cancers correlate with poor patient prognosis and with drug resistance. Therefore, these antioxidants represent a potential new target for chemotherapy treatments, especially the thioredoxin reductase (TrxR) protein, which can be targeted through its selenocysteine residue. Inhibition of TrxR leads to increased ROS levels in cancer cells to a lethal level, consequently leading to activation of cell death mechanisms. However, ROS levels remain at non-lethal levels in normal cells, thus enabling specific targeting of cancer cells. The design and availability of inhibitors for the specific upregulated antioxidant proteins in each type of cancer may also overcome drug resistance by resensitizing cancers to existing chemotherapy treatments.
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View more >Most cancer cells contain high levels of reactive oxygen species (ROS), which result in higher expression levels of the glutathione and thioredoxin reductase systems. These antioxidant systems convert ROS to non-harmful compounds and they also reduce disulphide bonds in oxidised proteins. They also control the glutathionylation and nitrosylation of proteins, which alters the activity of the proteins. Through these functions the upregulated antioxidant systems act on transcription factors and on signalling pathways, which results in the promotion of cancer cell growth and the prevention of cell apoptosis. High levels of certain members of the glutathione and thioredoxin systems in specific cancers correlate with poor patient prognosis and with drug resistance. Therefore, these antioxidants represent a potential new target for chemotherapy treatments, especially the thioredoxin reductase (TrxR) protein, which can be targeted through its selenocysteine residue. Inhibition of TrxR leads to increased ROS levels in cancer cells to a lethal level, consequently leading to activation of cell death mechanisms. However, ROS levels remain at non-lethal levels in normal cells, thus enabling specific targeting of cancer cells. The design and availability of inhibitors for the specific upregulated antioxidant proteins in each type of cancer may also overcome drug resistance by resensitizing cancers to existing chemotherapy treatments.
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Book Title
Handbook of Oxidative Stress in Cancer: Mechanistic Aspects
Copyright Statement
© 2021 Springer. This is the author-manuscript version of this paper. It is reproduced here in accordance with the copyright policy of the publisher. Please refer to the publisher’s website for further information.
Subject
Biochemistry and cell biology not elsewhere classified
Oncology and carcinogenesis not elsewhere classified