title: Effects of flavored mineral waters on AhR-CYP1A1 signaling pathway in primary human hepatocytes and in human hepatic and intestinal cancer cells.
abstract: Food-drug interaction is an emerging phenomenon, comprising pharmacokinetic or toxicokinetic interactions between food constituents and drugs. The mechanisms include inhibition of enzymes and transporters, and induction of drug metabolizing enzymes. A prominent regulator of drug-metabolizing enzymes is an aryl hydrocarbon receptor (AhR) that transcriptionally regulates CYP1 enzymes, phase II enzymes and many other genes. In the current paper, we have examined the effects of 28 different flavored mineral waters on AhR-CYP1A1 signaling pathway in primary cultures of human hepatocytes and in human cancer cell lines HepG2 (hepatic) and LS174T (intestinal). The techniques of Western blot, RT-PCR and gene reporter assays were employed to determine the expression of CYP1A1 mRNA, protein and activation of AhR, respectively. We have identified four flavored mineral waters which activated AhR and/or induced CYP1A1. These data imply a potential of some flavored mineral waters to cause food-drug interactions. In addition, activation of AhR-CYP1A1 signaling may result in chemically-induced carcinogenesis and alteration of intermediary metabolism.
authors.affiliation: Department of Cell Biology and Genetics, Faculty of Science, Palacky University Olomouc, Slechtitelu 11, 783 71 Olomouc, Czech Republic.
authors.forename: Alzbeta
authors.initials: A
authors.lastname: Kamenickova
authors.forename: Zdenek
authors.initials: Z
authors.lastname: Dvorak
mesh_terms: D015153:Blotting, Western; D045744:Cell Line, Tumor; D019363:Cytochrome P-450 CYP1A1 / Q000502:physiology*; D019388:Cytochrome P-450 CYP1A2 / Q000502:physiology; D018565:Food-Drug Interactions; D017930:Genes, Reporter / Q000187:drug effects; D022781:Hepatocytes / Q000187:drug effects*; D006801:Humans; D007414:Intestinal Neoplasms / Q000473:pathology; D008113:Liver Neoplasms / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008900:Mineral Waters; D060888:Real-Time Polymerase Chain Reaction; D018336:Receptors, Aryl Hydrocarbon / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D008900:Mineral Waters; D018336:Receptors, Aryl Hydrocarbon; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2