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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doaj-bf9d9191d7de4caa8ee29bcbdb8cc7892020-11-24T23:44:54ZengHindawi LimitedInternational Journal of Cell Biology1687-88761687-88842012-01-01201210.1155/2012/486147486147The Yin and Yang of Nrf2-Regulated Selenoproteins in CarcinogenesisRegina Brigelius-Flohé0Mike Müller1Doris Lippmann2Anna Patricia Kipp3Department Biochemistry of Micronutrients, German Institute of Human Nutrition, Potsdam-Rehbruecke, Arthur-Scheunert-Allee 114-116, 14558 Nuthetal, GermanyDepartment Biochemistry of Micronutrients, German Institute of Human Nutrition, Potsdam-Rehbruecke, Arthur-Scheunert-Allee 114-116, 14558 Nuthetal, GermanyDepartment Biochemistry of Micronutrients, German Institute of Human Nutrition, Potsdam-Rehbruecke, Arthur-Scheunert-Allee 114-116, 14558 Nuthetal, GermanyDepartment Biochemistry of Micronutrients, German Institute of Human Nutrition, Potsdam-Rehbruecke, Arthur-Scheunert-Allee 114-116, 14558 Nuthetal, GermanyThe 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.http://dx.doi.org/10.1155/2012/486147 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Regina Brigelius-Flohé Mike Müller Doris Lippmann Anna Patricia Kipp |
spellingShingle |
Regina Brigelius-Flohé Mike Müller Doris Lippmann Anna Patricia Kipp The Yin and Yang of Nrf2-Regulated Selenoproteins in Carcinogenesis International Journal of Cell Biology |
author_facet |
Regina Brigelius-Flohé Mike Müller Doris Lippmann Anna Patricia Kipp |
author_sort |
Regina Brigelius-Flohé |
title |
The Yin and Yang of Nrf2-Regulated Selenoproteins in Carcinogenesis |
title_short |
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_sort |
yin and yang of nrf2-regulated selenoproteins in carcinogenesis |
publisher |
Hindawi Limited |
series |
International Journal of Cell Biology |
issn |
1687-8876 1687-8884 |
publishDate |
2012-01-01 |
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. |
url |
http://dx.doi.org/10.1155/2012/486147 |
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