title: Effects of artificial sweeteners on the AhR- and GR-dependent CYP1A1 expression in primary human hepatocytes and human cancer cells.
abstract: Food constituents may cause a phenomenon of food-drug interactions. In the current study, we examined the effects of artificial sweeteners (aspartame, acesulfame, cyclamate, saccharin) on the aryl hydrocarbon receptor (AhR) and glucocorticoid receptor (GR)-dependent expression of CYP1A1 in human hepatocytes, hepatic HepG2 and intestinal LS174T cancer cell lines. Sweeteners were tested in concentrations up to those occurring in non-alcoholic beverages. Basal and ligand-inducible AhR- and GR-dependent reporter gene activation in stably transfected HepG2 and HeLa cells, respectively, were not affected by either of the sweeteners tested after 24h of incubation. The expression of CYP1A1 mRNA and protein in primary cultures of human hepatocytes and in LS174T and HepG2 cells was not induced by any of the tested sweeteners. Overall, aspartame, acesulfame, saccharin and cyclamate had no effects on CYP1A1 expression and transcriptional activities of AhR and GR. These data imply the safety of artificial sweeteners in terms of interference with AhR, GR and CYP1A1.
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: Michaela
authors.initials: M
authors.lastname: Pecova
authors.forename: Petr
authors.initials: P
authors.lastname: Bachleda
authors.forename: Zdenek
authors.initials: Z
authors.lastname: Dvorak
mesh_terms: D001218:Aspartame / Q000494:pharmacology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003494:Cyclamates / Q000494:pharmacology; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics / Q000378:metabolism*; D018565:Food-Drug Interactions; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism*; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D012439:Saccharin / Q000494:pharmacology; D013549:Sweetening Agents / Q000494:pharmacology*; D013843:Thiazines / Q000494:pharmacology
chemical_list: D003494:Cyclamates; D018336:Receptors, Aryl Hydrocarbon; D011965:Receptors, Glucocorticoid; D013549:Sweetening Agents; D013843:Thiazines; C569463:CYP1A1 protein, human; D019363:Cytochrome P-450 CYP1A1; D012439:Saccharin; C006362:acetosulfame; D001218:Aspartame
keywords: 2,3,7,8-tetrachlorodibenzo-p-dioxin; AhR; Artificial sweeteners; Aryl hydrocarbon Receptor; Aryl hydrocarbon receptor; CAR; Constitutive androstane receptor; Cytochrome P450; ER; Food–drug interactions; GR; Glucocorticoid receptor; LXR; PXR; RXR; TCDD; estrogen receptor; glucocorticoid receptor; liver X receptor; pregnane X receptor; retinoic X receptor