The Yin and Yang of Nrf2-Regulated Selenoproteins in CarcinogenesisReport as inadecuate

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International Journal of Cell BiologyVolume 2012 2012, Article ID 486147, 8 pages

Review ArticleDepartment Biochemistry of Micronutrients, German Institute of Human Nutrition, Potsdam-Rehbruecke, Arthur-Scheunert-Allee 114-116, 14558 Nuthetal, Germany

Received 1 February 2012; Accepted 20 February 2012

Academic Editor: Giuseppe Filomeni

Copyright © 2012 Regina Brigelius-Flohé et al. 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.


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.

Author: Regina Brigelius-Flohé, Mike Müller, Doris Lippmann, and Anna Patricia Kipp



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