title: Effects of anthocyanins on the AhR-CYP1A1 signaling pathway in human hepatocytes and human cancer cell lines.
abstract: Anthocyanins are plant pigments occurring in flowers and berry fruits. Since a phenomenon of food-drug interactions is increasingly emerging, we examined the effects of 21 major anthocyanins and the extracts from 3 food supplements containing anthocyanins on the aryl hydrocarbon receptor (AhR)-cytochrome P450 CYP1A1 signaling pathway in human hepatocytes and human hepatic HepG2 and intestinal LS174T cancer cells. Pelargonidin-3-O-rutinoside (PEL-2) and cyanidin-3,5-O-diglucoside (CYA-3) dose-dependently activated AhR, as revealed by gene reporter assay. PEL-2 and CYA-3 induced CYP1A1 mRNA but not protein in HepG2 and LS174T cells. Neither compounds induced CYP1A1 mRNA and protein in four different primary human hepatocytes cultures. The effects of PEL-2 and CYA-3 on AhR occurred by ligand-dependent and ligand-independent mechanisms, respectively, as demonstrated by ligand binding assay. In a direct enzyme inhibition assay, none of the antocyanins tested inhibited the CYP1A1 marker activity to less than 50% even at 100 μM concentration. PEL-2 and CYA-3 at 100 μM inhibited CYP1A1 to 79% and 65%, respectively. In conclusion, with exception of PEL-2 and CYA-3, there were no effects of 19 major anthocyanins and 3 food supplements containing anthocyanins on AhR-CYP1A1 signaling, implying zero potential of these compounds for food-drug interactions with respect to AhR-CYP1A1 pathway.
authors.affiliation: Department of Cell Biology and Genetics, Faculty of Science, Palacky University, Slechtitelu 11, 783 71 Olomouc, Czech Republic.
authors.forename: Alzbeta
authors.initials: A
authors.lastname: Kamenickova
authors.forename: Eva
authors.initials: E
authors.lastname: Anzenbacherova
authors.forename: Petr
authors.initials: P
authors.lastname: Pavek
authors.forename: Anatoly A
authors.initials: AA
authors.lastname: Soshilov
authors.forename: Michael S
authors.initials: MS
authors.lastname: Denison
authors.forename: Michaela
authors.initials: M
authors.lastname: Zapletalova
authors.forename: Pavel
authors.initials: P
authors.lastname: Anzenbacher
authors.forename: Zdenek
authors.initials: Z
authors.lastname: Dvorak
mesh_terms: D000328:Adult; D000872:Anthocyanins / Q000737:chemistry / Q000633:toxicity*; D002470:Cell Survival / Q000187:drug effects; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism*; D019587:Dietary Supplements; D004791:Enzyme Inhibitors / Q000633:toxicity; D005260:Female; D018565:Food-Drug Interactions; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005960:Glucosides / Q000737:chemistry / Q000633:toxicity; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D008875:Middle Aged; D011485:Protein Binding; D018336:Receptors, Aryl Hydrocarbon / Q000187:drug effects* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000872:Anthocyanins; D004791:Enzyme Inhibitors; D005960:Glucosides; D018336:Receptors, Aryl Hydrocarbon; C462279:cyanidin-3-O-beta-glucopyranoside; C066957:pelargonidin; D019363:Cytochrome P-450 CYP1A1
keywords: 2,3,7,8-tetrachlorodibenzo-p-dioxin; AhR; Anthocyanins; Aryl hydrocarbon receptor; Cytochrome P450; Food supplements; Food–drug interactions; TCDD; aryl hydrocarbon receptor