title: TrxR1 and GPx2 are potently induced by isothiocyanates and selenium, and mutually cooperate to protect Caco-2 cells against free radical-mediated cell death.
abstract: Currently, there is significant interest in the field of diet-gene interactions and the mechanisms by which food compounds regulate gene expression to modify cancer susceptibility. From a nutrition perspective, two key components potentially exert cancer chemopreventive effects: isothiocyanates (ITCs), present in cruciferous vegetables, and selenium (Se) which, as selenocysteine, is an integral part of selenoproteins. However, the role of these compounds in the expression of key selenoenzymes once the cancer process has been initiated still needs elucidation. Therefore, this investigation examined the effect of two forms of selenium, selenium-methylselenocysteine and sodium selenite, both individually and in combination with two ITCs, sulforaphane or iberin, on the expression of the two selenoenzymes, thioredoxin reductase 1 (TrxR1) and gastrointestinal glutathione peroxidase (GPx2), which are targets of ITCs, in Caco-2 cells. Co-treatment with both ITCs and Se induced expression of TrxR1 and GPx2 more than either compound alone. Moreover, pre-treatment of cells with ITC+Se enhanced cytoprotection against H(2)O(2)-induced cell death through a ROS-dependent mechanism. Furthermore, a single and double knockdown of TrxR1 and/or GPx2 suggested that both selenoproteins were responsible for protecting against H(2)O(2)-induced cell death. Together, these data shed new light on the mechanism of interactions between ITC and Se in which translational expression of the enhanced transcripts by the former is dependent on an adequate Se supply, resulting in a cooperative antioxidant protective effect against cell death.
authors: Department of Nutrition, Norwich Medical School, University of East Anglia, Norwich, UK.
authors: Lawrence N
authors: LN
authors: Barrera
authors: Aedin
authors: A
authors: Cassidy
authors: Wei
authors: W
authors: Wang
authors: Taotao
authors: T
authors: Wei
authors: Nigel J
authors: NJ
authors: Belshaw
authors: Ian T
authors: IT
authors: Johnson
authors: Regina
authors: R
authors: Brigelius-Flohé
authors: Yongping
authors: Y
authors: Bao
mesh_terms: D018938:Caco-2 Cells; D016923:Cell Death / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D019610:Cytoprotection / Q000187:drug effects*; D019587:Dietary Supplements; D004790:Enzyme Induction / Q000187:drug effects; D005609:Free Radicals / Q000633:toxicity*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D055785:Gene Knockdown Techniques; D005979:Glutathione Peroxidase / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D015151:Immunoblotting; D017879:Isothiocyanates / Q000494:pharmacology*; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D014176:Protein Biosynthesis / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D012643:Selenium / Q000494:pharmacology*; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism; D054481:Thioredoxin Reductase 1 / Q000096:biosynthesis* / Q000235:genetics; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
chemical_list: D005609:Free Radicals; D017879:Isothiocyanates; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D006861:Hydrogen Peroxide; C117436:GPX2 protein, human; D005979:Glutathione Peroxidase; C516124:TXNRD1 protein, human; D054481:Thioredoxin Reductase 1; D012643:Selenium