Cited by 589Redox biology and oxidative stressSelenium in Biological SystemsGenomics, phytochemicals, and oxidative stress

The thioredoxin system in cancer

Arnér, Elias S.J., Holmgren, Arne·2006·Seminars in Cancer Biology

Abstract

Thioredoxin (Trx), NADPH and thioredoxin reductase (TrxR) comprise a thioredoxin system which exists in nearly all living cells. It functions in thiol-dependent thiol-disulfide exchange reactions crucial to control of the reduced intracellular redox environment, cellular growth, defense against oxidative stress or control of apoptosis and has multi-facetted roles in mammalian cells including implications in cancer. Eg reduced Trx activates DNA binding of transcription factors and is involved in antioxidant defense through repair of oxidatively damaged proteins or as an electron donor to peroxiredoxins. The Trx system functions in synthesis of deoxyribonucleotides for DNA synthesis, both replication and repair, by ribonucleotide reductase. Trx and truncated Trx (Trx80) act in modulation of immune cell function. TrxR isoforms in the cytosol and the mitochondria are essential selenoenzymes with a selenocysteine in the active site. These enzymes display a remarkably broad substrate specificity but are also targets for existing chemotherapeutic drugs. Mammalian TrxR enzymes are linked to selenium metabolism as a result of being selenoproteins, but can also directly reduce low molecular selenium compounds like selenite and have been implicated in the chemoprevention effects of selenium against cancer. Numerous scientific reports describe higher expression of Trx and TrxR in some, but not all tumors. Some data suggest that high Trx could be linked to resistance to chemotherapies while others suggest that high Trx and TrxR may induce apoptosis and reduce the mitotic index of certain tumors linked to the p53 dependent cell death. Recent data suggest that TrxR is essential for the carcinogenic process and invasive phenotype of cancer. Both Trx and TrxR have been regarded as interesting targets for chemotherapy.

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Crossref · 10.1016/j.semcancer.2006.10.009

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Authors
Arnér, E. S. J., & Holmgren, A.
Affiliations
Karolinska Institutet (SE)
Corresponding author
Arnér, Elias S.J.
Venue
Seminars in Cancer Biology
Publisher
Elsevier BV
Published
2006-12
Volume
16
Issue
6
Pages
420-426
ISSN
1044-579X (ISSN-L)
OpenAlex
W2003675056
Cited by
589
References
93
Citations by year
2026: 24 · 2025: 21 · 2024: 29 · 2023: 24 · 2022: 30 · 2021: 20 · 2020: 32 · 2019: 26 · 2018: 28 · 2017: 32 · 2016: 34 · 2015: 39 · 2014: 38 · 2013: 20 · 2012: 30
FWCI
2.62
Type
journal article
Language
en
Open access
closed
Locations
  • Seminars in Cancer Biology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
  • Health Sciences › Nursing › Nutrition and Dietetics › Selenium in Biological Systems
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics, phytochemicals, and oxidative stress
Keywords
thioredoxin system, thioredoxin, thioredoxin reductase, cancer, redox homeostasis, thiol-disulfide exchange, selenoproteins, selenocysteine, selenium metabolism, chemoresistance, apoptosis, p53-dependent cell death, ribonucleotide reductase, DNA synthesis, oxidative stress, tumor invasion, chemotherapeutic target
MeSH terms
Humans, Neoplasms, Thioredoxins

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