title: Antioxidative dietary compounds modulate gene expression associated with apoptosis, DNA repair, inhibition of cell proliferation and migration.
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.
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China. wonalbert69@gmail.com.
authors.forename: Likui
authors.initials: L
authors.lastname: Wang
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China. gao_shijuan@163.com.
authors.forename: Shijuan
authors.initials: S
authors.lastname: Gao
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China. jiangw@im.ac.cn.
authors.forename: Wei
authors.initials: W
authors.lastname: Jiang
authors.affiliation: Department of Biotechnology, University of Tartu, Tartu 51010, Estonia. markus.rosendahl@gmail.com.
authors.forename: Cheng
authors.initials: C
authors.lastname: Luo
authors.affiliation: Department of Food and Environmental Sciences, Division of Food Chemistry, University of Helsinki, Helsinki F-00014, Finland. xumaonian@gmail.com.
authors.forename: Maonian
authors.initials: M
authors.lastname: Xu
authors.affiliation: Division of Pharmacognosy, Department of Medicinal Chemistry, Biomedical Center University of Uppsala, Uppsala 75123, Sweden. lars.bohlin@fkog.uu.se.
authors.forename: Lars
authors.initials: L
authors.lastname: Bohlin
authors.affiliation: Mysenso Oy, Hollola 15870, Finland. markus.rosendahl@gmail.com.
authors.forename: Markus
authors.initials: M
authors.lastname: Rosendahl
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China. wl_huang@hotmail.com.
authors.forename: Wenlin
authors.initials: W
authors.lastname: Huang
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004260:DNA Repair / Q000187:drug effects*; D004032:Diet; D006801:Humans
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D051546:Cyclooxygenase 2