title: The long chain α-tocopherol metabolite α-13'-COOH and γ-tocotrienol induce P-glycoprotein expression and activity by activation of the pregnane X receptor in the intestinal cell line LS 180.
abstract: Members of the vitamin E family or their metabolites may induce the xenobiotic transporter P-glycoprotein (P-gp), which can limit the bioavailability of drugs and phytochemicals. This study aimed to investigate if α- and γ-tocopherol, α- and γ-tocotrienol, the long chain metabolite α-tocopherol-13'-COOH, the short chain metabolites α- and γ-carboxyethylhydroxychromanol and plastochromanol-8 activate the pregnane X receptor (PXR) and thereby modulate P-gp expression and/or activity.
  
  
  
  P-gp protein expression and activity were studied in LS 180 cells incubated with the respective test compound for 48 h. Furthermore, we determined if the compounds activate PXR in LS 180 cells, as PXR regulates P-gp expression. Neither P-gp protein expression and activity, nor PXR activity were influenced by α-tocopherol, γ-tocopherol and plastochromanol-8. α-Tocotrienol activated PXR in the reporter gene assay but did not induce protein expression or activity of P-gp. γ-Tocotrienol and α-13'-COOH activated PXR and induced protein expression and transporter activity of P-gp.
  
  
  
  Because the induction of P-gp in the intestine may limit the systemic bioavailability of its substrates, the concurrent intake of drugs and γ-tocotrienol and, if ever applicable, α-13'-COOH should be avoided.
authors.affiliation: Institute of Biological Chemistry and Nutrition, University of Hohenheim, Stuttgart, Germany.
authors.forename: Maren C
authors.initials: MC
authors.lastname: Podszun
authors.affiliation: Institute of Biological Chemistry and Nutrition, University of Hohenheim, Stuttgart, Germany.
authors.forename: Metta
authors.initials: M
authors.lastname: Jakobi
authors.affiliation: Department of Nutritional, Food and Consumer, University of Applied Sciences, Fulda, Germany.
authors.forename: Marc
authors.initials: M
authors.lastname: Birringer
authors.affiliation: Department of Clinical Pharmacology and Pharmacoepidemiology, University Hospital Heidelberg, Germany.
authors.forename: Johanna
authors.initials: J
authors.lastname: Weiss
authors.affiliation: Institute of Biological Chemistry and Nutrition, University of Hohenheim, Stuttgart, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Frank
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D001578:Benzopyrans / Q000378:metabolism / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002839:Chromans / Q000378:metabolism / Q000494:pharmacology*; D005227:Fatty Acids / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D007422:Intestines; D000077297:Pregnane X Receptor; D011987:Receptors, Steroid / Q000235:genetics / Q000378:metabolism*; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D024502:alpha-Tocopherol / Q000493:pharmacokinetics; D024504:gamma-Tocopherol / Q000493:pharmacokinetics
chemical_list: C000607530:13'-(6-hydroxy-2,5,7,8,-tetramethylchroman-2-yl)-2,6,10-trimethyltridecanoic acid; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D001578:Benzopyrans; D002839:Chromans; D005227:Fatty Acids; D000077297:Pregnane X Receptor; D011987:Receptors, Steroid; D014810:Vitamin E; C013649:plastochromanol 8; D024504:gamma-Tocopherol; D024502:alpha-Tocopherol
keywords: Alpha-13’-COOH; Alpha-tocopherol; PC-8, P-glycoprotein; PXR / Vitamin E