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Int. J. Mol. Sci. 2014, 15(9), 16226-16245; doi:10.3390/ijms150916226

Antioxidative Dietary Compounds Modulate Gene Expression Associated with Apoptosis, DNA Repair, Inhibition of Cell Proliferation and Migration

1
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China
2
Department of Biotechnology, University of Tartu, Tartu 51010, Estonia
3
Mysenso Oy, Hollola 15870, Finland
4
Department of Food and Environmental Sciences, Division of Food Chemistry, University of Helsinki, Helsinki F-00014, Finland
5
Division of Pharmacognosy, Department of Medicinal Chemistry, Biomedical Center University of Uppsala, Uppsala 75123, Sweden
6
State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-Sen University, Guangzhou 510060, China
*
Authors to whom correspondence should be addressed.
Received: 16 June 2014 / Revised: 21 July 2014 / Accepted: 27 August 2014 / Published: 15 September 2014
(This article belongs to the Special Issue DNA Damage and Repair in Degenerative Diseases 2014)
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Abstract

Many dietary compounds are known to have health benefits owing to their antioxidative and anti-inflammatory properties. To determine the molecular mechanism of these food-derived compounds, we analyzed their effect on various genes related to cell apoptosis, DNA damage and repair, oxidation and inflammation using in vitro cell culture assays. This review further tests the hypothesis proposed previously that downstream products of COX-2 (cyclooxygenase-2) called electrophilic oxo-derivatives induce antioxidant responsive elements (ARE), which leads to cell proliferation under antioxidative conditions. Our findings support this hypothesis and show that cell proliferation was inhibited when COX-2 was down-regulated by polyphenols and polysaccharides. Flattened macrophage morphology was also observed following the induction of cytokine production by polysaccharides extracted from viili, a traditional Nordic fermented dairy product. Coix lacryma-jobi (coix) polysaccharides were found to reduce mitochondrial membrane potential and induce caspase-3- and 9-mediated apoptosis. In contrast, polyphenols from blueberries were involved in the ultraviolet-activated p53/Gadd45/MDM2 DNA repair system by restoring the cell membrane potential. Inhibition of hypoxia-inducible factor-1 by saponin extracts of ginsenoside (Ginsen) and Gynostemma and inhibition of S100A4 by coix polysaccharides inhibited cancer cell migration and invasion. These observations suggest that antioxidants and changes in cell membrane potential are the major driving forces that transfer signals through the cell membrane into the cytosol and nucleus, triggering gene expression, changes in cell proliferation and the induction of apoptosis or DNA repair. View Full-Text
Keywords: anti-inflammatory; antioxidants; apoptosis; cell migration and invasion; DNA repair anti-inflammatory; antioxidants; apoptosis; cell migration and invasion; DNA repair
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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MDPI and ACS Style

Wang, L.; Gao, S.; Jiang, W.; Luo, C.; Xu, M.; Bohlin, L.; Rosendahl, M.; Huang, W. Antioxidative Dietary Compounds Modulate Gene Expression Associated with Apoptosis, DNA Repair, Inhibition of Cell Proliferation and Migration. Int. J. Mol. Sci. 2014, 15, 16226-16245.

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