ISPG/IIA Studentship: Chemo-protective effects of dietary isothiocyantes and selenium
Lead Research Organisation:
QUADRAM INSTITUTE BIOSCIENCE
Department Name: UNLISTED
Abstract
Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.
Technical Summary
This study will investigate if a combination of selenium and isothiocyanates in cultured cells systems (human colon adenocarcinoma Caco-2 and hepatoma HepG2 cells) will offer additive or synergistic effects to improve antioxidant capacity. It will also allow us to determine the impact of these food components on epigenetic events such as DNA methylation and/or histone regulation, helping to identify changes in the regulation of gene expression.
Planned Impact
unavailable
People |
ORCID iD |
| Ian Johnson (Principal Investigator) | |
| Nigel Belshaw (Co-Investigator) |
Publications
Barrera LN
(2013)
Colorectal cancer cells Caco-2 and HCT116 resist epigenetic effects of isothiocyanates and selenium in vitro.
in European journal of nutrition
Barrera LN
(2012)
Epigenetic and antioxidant effects of dietary isothiocyanates and selenium: potential implications for cancer chemoprevention.
in The Proceedings of the Nutrition Society
Barrera LN
(2012)
TrxR1 and GPx2 are potently induced by isothiocyanates and selenium, and mutually cooperate to protect Caco-2 cells against free radical-mediated cell death.
in Biochimica et biophysica acta
Méplan C
(2016)
Transcriptomics and proteomics show that selenium affects inflammation, cytoskeleton, and cancer pathways in human rectal biopsies.
in FASEB journal : official publication of the Federation of American Societies for Experimental Biology
| Description | 1. High consumption of cruciferous vegetables may protect against specific cancers in human beings. These beneficial effects are attributed to the glucosinolate breakdown products, isothiocyanates (ITC). Similarly, selenium (Se) consumption has also been inversely associated with cancer risk and, as an integral part of many selenoproteins, may influence multiple pathways in the development of cancer. This project sought to explore the hypothesis that a combination of ITC and Se may act synergistically to protect cells against alterations leading to neoplasia. We 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. 2. 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. 3. 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. 4. 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. |
| Exploitation Route | These results have the potential to inform new dietary and pharmacological strategies for chemoprevention against cancer in human populations. |
| Sectors | Agriculture Food and Drink Chemicals Healthcare Pharmaceuticals and Medical Biotechnology |
| Description | There is evidence from epidemiological studies suggesting that increased consumption of cruciferous vegetables may protect against specific cancers in human beings. These beneficial effects are attributed to the glucosinolate breakdown products, isothiocyanates (ITC). Similarly, selenium (Se) consumption has also been inversely associated with cancer risk and, as an integral part of many selenoproteins, may influence multiple pathways in the development of cancer. This project provided evidence to support the hypothesis that a combination of ITC and Se may act synergistically to protect cells against alterations leading to neoplasia. An understanding of the impact of ITC and Se on aberrant DNA methylation, in addition to the effect of these food constituents as modulators of key selenoenzymes such as gastrointestinal glutathione peroxidase-2 (GPx2) and thioredoxin reductase-1 (TrxR1), may provide new strategies for the development of plant-based diets, or dietary supplements, to counteract the genetic and epigenetic alterations that initiate and sustain neoplasia. |
| First Year Of Impact | 2011 |
| Sector | Agriculture, Food and Drink,Chemicals,Healthcare,Pharmaceuticals and Medical Biotechnology |
| Impact Types | Societal |