Part of the Series: From dietary antioxidants to regulators in cellular signaling and gene regulation
- 1 January 2006
- journal article
- review article
- Published by Taylor & Francis in Free Radical Research
- Vol. 40 (8) , 775-787
- https://doi.org/10.1080/10715760600722643
Abstract
The association of decreased cancer risk with intake of cruciferous vegetables and selenium is stronger than that reported for fruits and vegetables in general. An active constituent in cruciferae is sulforaphane. Chemopreventive effects of both, sulforaphane and selenium have been attributed to an antioxidant action which certainly is too simplicistic. Sulforaphane induces via activation of the Nrf2/Keap1 system phase 2 enzymes that protect against carcinogens and oxidants. Induced enzymes comprise the selenoproteins thioredoxin reductase-1 (TrxR1) and gastrointestinal glutathione peroxidase (GI-GPx, GPx2), which contain antioxidant response elements (ARE) in their promoter regions. Translational realisation of the enhanced transcripts depends on adequate selenium supply, which explains the synergism of Nrf2 activators and selenium. Regarding tumorigenesis the role of TrxR1 is ambiguous: it is essential for fast tumor cell growth but also diminishes vascularisation of tumors. The anticarcinogenic role of GI-GPx is evident from enhanced gastrointestinal tumor formation in gpx2/gpx1 double KO mice.Keywords
This publication has 123 references indexed in Scilit:
- Nuclear Import and Export Signals in Control of Nrf2Journal of Biological Chemistry, 2005
- Ubiquitination of Keap1, a BTB-Kelch Substrate Adaptor Protein for Cul3, Targets Keap1 for Degradation by a Proteasome-independent PathwayJournal of Biological Chemistry, 2005
- Keap1, the Sensor for Electrophiles and Oxidants that Regulates the Phase 2 Response, Is a Zinc MetalloproteinBiochemistry, 2005
- Expression of Gastrointestinal Glutathione Peroxidase Is Inversely Correlated to the Presence of Hepatitis C Virus Subgenomic RNA in Human Liver CellsJournal of Biological Chemistry, 2005
- Induction of thioredoxin reductase as an adaptive response to acrolein in human umbilical vein endothelial cellsBiochemical and Biophysical Research Communications, 2005
- Consumption of Vegetables and Fruits and Risk of Breast CancerJAMA, 2005
- Thioredoxin-dependent redox regulation of the antioxidant responsive element (ARE) in electrophile responseOncogene, 2003
- Synergy between sulforaphane and selenium in the induction of thioredoxin reductase 1 requires both transcriptional and translational modulationCarcinogenesis: Integrative Cancer Research, 2003
- Degradation of Transcription Factor Nrf2 via the Ubiquitin-Proteasome Pathway and Stabilization by CadmiumJournal of Biological Chemistry, 2003
- Global cancer statistics in the year 2000The Lancet Oncology, 2001