| GSTT2, a phase II gene induced by apple polyphenols, protects colon epithelial cells against genotoxic damage. | |
| | |
MedLine Citation:
|
PMID: 19753610 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
The potential protective effect of a polyphenol-rich diet for colon carcinogenesis is of great scientific and medical interest. Apples are a main source of polyphenols, and apple juice has been shown to attenuate chemically induced colon carcinogenesis in animal models. In addition to an antioxidant and antiproliferative activity, apple polyphenols have been shown to elevate expression of the phase II gene glutathione S-transferase T2 (GSTT2) in colon epithelial cells. We hypothesized that apple polyphenols may thereby provide protection against oxidant-induced DNA damage. Using GSTT2 promoter constructs and luciferase reporter assays, we found that polyphenolic apple extracts (AE) can directly enhance GSTT2 promoter activity. Comet assays demonstrated that the genotoxicity of the GSTT2 substrate cumene hydroperoxide (CumOOH) was significantly reduced when HT29 colon epithelial cells were pretreated with AE. Overexpression of GSTT2 in HT29 cells significantly reduced CumOOH induced DNA damage, whereas shRNA mediated knockdown of GSTT2 gene expression resulted in higher damage. Our results causally link GSTT2 levels with protection from genotoxic stress, and provide evidence that the antigenotoxic effects of apple polyphenols in vitro are at least in part due to an induction of GSTT2 expression. Induction of phase II genes may contribute to primary chemoprevention of colon cancer by apple polyphenols. |
| | |
Authors:
|
Astrid Petermann; Claudia Miene; Gabriele Schulz-Raffelt; Katja Palige; Jana H?lzer; Michael Glei; Frank-D B?hmer |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
|
Title: Molecular nutrition & food research Volume: 53 ISSN: 1613-4133 ISO Abbreviation: Mol Nutr Food Res Publication Date: 2009 Oct |
Date Detail:
|
Created Date: 2009-10-07 Completed Date: 2010-02-17 Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 101231818 Medline TA: Mol Nutr Food Res Country: Germany |
Other Details:
|
Languages: eng Pagination: 1245-53 Citation Subset: IM |
Affiliation:
|
Center for Molecular Biomedicine, Institute of Molecular Cell Biology, Friedrich-Schiller-University Jena, Germany. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Anticarcinogenic Agents
/
pharmacology* Benzene Derivatives / toxicity Cell Line Colon / drug effects, metabolism Comet Assay DNA Damage* Flavonoids / pharmacology* Fruit / chemistry Gene Expression Regulation, Enzymologic Gene Knockdown Techniques Genes, Reporter Glutathione Transferase / biosynthesis, genetics*, metabolism HT29 Cells Humans Hydrogen Peroxide / analysis Intestinal Mucosa / drug effects, metabolism* Malus / chemistry* Oxidants / toxicity Phenols / pharmacology* Plant Extracts / pharmacology* Promoter Regions, Genetic RNA, Small Interfering |
| Chemical | |
Reg. No./Substance:
|
0/Anticarcinogenic Agents; 0/Benzene Derivatives; 0/Flavonoids; 0/Oxidants; 0/Phenols; 0/Plant Extracts; 0/RNA, Small Interfering; 0/polyphenols; 7722-84-1/Hydrogen Peroxide; 80-15-9/cumene hydroperoxide; EC 2.5.1.-/GSTT2 protein, human; EC 2.5.1.18/Glutathione Transferase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: High sensitivity detection of the glial fibrillary acidic protein as indicator for TSE risk material...
Next Document: Modification of pulse sequences reduces occupational exposure from MRI switched gradient fields: Pre...