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The Yin and Yang of Nrf2-Regulated Selenoproteins in Carcinogenesis

The NF-E2-related factor-2 (Nrf2) is a transcription factor which regulates the major cellular defense systems and thereby contributes to the prevention of many diseases including cancer. Selenium deficiency is associated with a higher cancer risk making also this essential trace element a promising...

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Autores principales: Brigelius-Flohé, Regina, Müller, Mike, Lippmann, Doris, Kipp, Anna Patricia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3357939/
https://www.ncbi.nlm.nih.gov/pubmed/22654914
http://dx.doi.org/10.1155/2012/486147
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author Brigelius-Flohé, Regina
Müller, Mike
Lippmann, Doris
Kipp, Anna Patricia
author_facet Brigelius-Flohé, Regina
Müller, Mike
Lippmann, Doris
Kipp, Anna Patricia
author_sort Brigelius-Flohé, Regina
collection PubMed
description The NF-E2-related factor-2 (Nrf2) is a transcription factor which regulates the major cellular defense systems and thereby contributes to the prevention of many diseases including cancer. Selenium deficiency is associated with a higher cancer risk making also this essential trace element a promising candidate for cancer prevention. Two selenoproteins, thioredoxin reductase-1 (TrxR1) and glutathione peroxidase-2 (GPx2), are targets for Nrf2. Selenium deficiency activates Nrf2 as does a TrxR1 knockout making a synergism between both systems plausible. Although this might hold true for healthy cells, the interplay may turn into the opposite in cancer cells. The induction of the detoxifying and antioxidant enzymes by Nrf2 will make cancer cells chemoresistant and will protect them against oxidative damage. The essential role of TrxR1 in maintaining proliferation makes its upregulation in cancer cells detrimental. The anti-inflammatory potential of GPx2 will help to inhibit cancer initiation and inflammation-triggered promotion, but its growth supporting potential will also support tumor growth. This paper considers beneficial and adverse consequences of the activation of Nrf2 and the selenoproteins which appear to depend on the cancer stage.
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spelling pubmed-33579392012-05-31 The Yin and Yang of Nrf2-Regulated Selenoproteins in Carcinogenesis Brigelius-Flohé, Regina Müller, Mike Lippmann, Doris Kipp, Anna Patricia Int J Cell Biol Review Article The NF-E2-related factor-2 (Nrf2) is a transcription factor which regulates the major cellular defense systems and thereby contributes to the prevention of many diseases including cancer. Selenium deficiency is associated with a higher cancer risk making also this essential trace element a promising candidate for cancer prevention. Two selenoproteins, thioredoxin reductase-1 (TrxR1) and glutathione peroxidase-2 (GPx2), are targets for Nrf2. Selenium deficiency activates Nrf2 as does a TrxR1 knockout making a synergism between both systems plausible. Although this might hold true for healthy cells, the interplay may turn into the opposite in cancer cells. The induction of the detoxifying and antioxidant enzymes by Nrf2 will make cancer cells chemoresistant and will protect them against oxidative damage. The essential role of TrxR1 in maintaining proliferation makes its upregulation in cancer cells detrimental. The anti-inflammatory potential of GPx2 will help to inhibit cancer initiation and inflammation-triggered promotion, but its growth supporting potential will also support tumor growth. This paper considers beneficial and adverse consequences of the activation of Nrf2 and the selenoproteins which appear to depend on the cancer stage. Hindawi Publishing Corporation 2012 2012-05-08 /pmc/articles/PMC3357939/ /pubmed/22654914 http://dx.doi.org/10.1155/2012/486147 Text en Copyright © 2012 Regina Brigelius-Flohé et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Review Article
Brigelius-Flohé, Regina
Müller, Mike
Lippmann, Doris
Kipp, Anna Patricia
The Yin and Yang of Nrf2-Regulated Selenoproteins in Carcinogenesis
title The Yin and Yang of Nrf2-Regulated Selenoproteins in Carcinogenesis
title_full The Yin and Yang of Nrf2-Regulated Selenoproteins in Carcinogenesis
title_fullStr The Yin and Yang of Nrf2-Regulated Selenoproteins in Carcinogenesis
title_full_unstemmed The Yin and Yang of Nrf2-Regulated Selenoproteins in Carcinogenesis
title_short The Yin and Yang of Nrf2-Regulated Selenoproteins in Carcinogenesis
title_sort yin and yang of nrf2-regulated selenoproteins in carcinogenesis
topic Review Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3357939/
https://www.ncbi.nlm.nih.gov/pubmed/22654914
http://dx.doi.org/10.1155/2012/486147
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