title: Coffee constituents as modulators of Nrf2 nuclear translocation and ARE (EpRE)-dependent gene expression.
abstract: Oxidative cellular stress initiates Nrf2 translocation into the nucleus, thus inducing antioxidant response element (ARE)-mediated expression of Phase II enzymes involved in detoxification and antioxidant defence. We investigated whether coffee extracts (CEs) of different proveniences and selected constituents have an impact on the Nrf2/ARE pathway in human colon carcinoma cells (HT29). Assessed as increased nuclear Nrf2 protein, Nrf2 nuclear translocation was modulated by different CEs as observed by Western blot analysis. In addition to the known Nrf2 activator 5-O-caffeoylquinic acid (CGA), pyridinium derivatives like the N-methylpyridinium ion (NMP) were identified as potent activators of Nrf2 nuclear translocation and ARE-dependent gene expression of selected antioxidative Phase II enzymes in HT29. Thereby, the substitution pattern at the pyridinium core structure determined the impact on Nrf2-signalling. In contrast, trigonelline was found to interfere with Nrf2 activation, effectively suppressing the NMP-mediated induction of Nrf2/ARE-dependent gene expression. In conclusion, several coffee constituents, partly already present in the raw material as well as those generated during the roasting process, contribute to the Nrf2-translocating properties of consumer-relevant coffee. A fine tuning in the degradation/formation of activating and deactivating constituents of the Nrf2/ARE pathway during the roasting process appears to be critical for the chemopreventive properties of the final coffee product.
authors.affiliation: Department of Food Chemistry and Toxicology, University of Vienna, Währinger Str. 38, A-1090 Vienna, Austria.
authors.forename: Ute
authors.initials: U
authors.lastname: Boettler
authors.forename: Katharina
authors.initials: K
authors.lastname: Sommerfeld
authors.forename: Nadine
authors.initials: N
authors.lastname: Volz
authors.forename: Gudrun
authors.initials: G
authors.lastname: Pahlke
authors.forename: Nicole
authors.initials: N
authors.lastname: Teller
authors.forename: Veronika
authors.initials: V
authors.lastname: Somoza
authors.forename: Roman
authors.initials: R
authors.lastname: Lang
authors.forename: Thomas
authors.initials: T
authors.lastname: Hofmann
authors.forename: Doris
authors.initials: D
authors.lastname: Marko
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology*; D015153:Blotting, Western; D002109:Caffeic Acids / Q000494:pharmacology; D002467:Cell Nucleus; D002726:Chlorogenic Acid / Q000032:analysis / Q000031:analogs & derivatives; D003069:Coffee / Q000737:chemistry*; D015870:Gene Expression / Q000187:drug effects*; D019073:HT29 Cells; D006801:Humans; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress; D010936:Plant Extracts / Q000494:pharmacology*; D021381:Protein Transport; D011726:Pyridinium Compounds / Q000378:metabolism; D011801:Quinic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D020218:Response Elements / Q000187:drug effects; D015398:Signal Transduction; D014158:Transcription, Genetic
chemical_list: D000970:Antineoplastic Agents; D000975:Antioxidants; D002109:Caffeic Acids; D002726:Chlorogenic Acid; D003069:Coffee; D051267:NF-E2-Related Factor 2; D010936:Plant Extracts; D011726:Pyridinium Compounds; D011801:Quinic Acid; C495635:NFE2L2 protein, human; C014677:1-methylpyridinium; C473200:5-caffeoylquinic acid