title: Differential inhibition by alpha- and beta-tocopherol of human erythroleukemia cell adhesion: role of integrins.
abstract: The effect of alpha- and beta-tocopherol on human erythroleukemia cell (HEL) adhesion induced by phorbol 12-myristate 13-acetate (PMA) has been studied. Adhesion induced by PMA stimulation was prevented by 44.5% by physiological concentrations of alpha-tocopherol. Under the same experimental conditions, beta-tocopherol, an analogue of alpha-tocopherol, produced 11% inhibition of adhesion. Cell response gradually increased from 0 to 24 h of alpha-tocopherol treatment. Only a slight time dependency of beta-tocopherol inhibition was observed. Another human erythroleukemia cell line (K562) and the human monocyte tumor cell line U937 showed 5.0 and 11.2% inhibition, respectively. Similar to alpha-tocopherol, the protein kinase C inhibitor, Calphostin C, and the MAPK inhibitor, PD98059, prevented PMA-induced cell adhesion. An inhibition of ERK-1 phosphorylation was observed for alpha-tocopherol only in HEL, implying that MAP kinase pathway is involved in this cell line. Fluorescence-activated cell sorting (FACS), by using various integrin-specific monoclonal antibodies, has shown that alpha (1-6), beta1, and alphav integrins are less expressed at the cell surface after alpha-tocopherol treatment. Beta-tocopherol treatment was less effective.
authors.affiliation: Institut für Biochemie und Molekularbiologie, Universität Bern, Bern, Switzerland.
authors.forename: I
authors.initials: I
authors.lastname: Breyer
authors.forename: A
authors.initials: A
authors.lastname: Azzi
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects*; D015536:Down-Regulation / Q000187:drug effects; D005419:Flavonoids / Q000494:pharmacology; D005434:Flow Cytometry; D006801:Humans; D016023:Integrins / Q000037:antagonists & inhibitors / Q000276:immunology / Q000502:physiology*; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000502:physiology; D020014:K562 Cells / Q000166:cytology / Q000187:drug effects*; D004915:Leukemia, Erythroblastic, Acute / Q000473:pathology*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D009281:Naphthalenes / Q000494:pharmacology; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000276:immunology / Q000502:physiology*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology; D051571:Protein Kinase C-alpha; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects; D020298:U937 Cells / Q000166:cytology / Q000187:drug effects*; D014810:Vitamin E / Q000494:pharmacology*
chemical_list: D000911:Antibodies, Monoclonal; D005419:Flavonoids; D016023:Integrins; D007527:Isoenzymes; D009281:Naphthalenes; D009363:Neoplasm Proteins; D014810:Vitamin E; C496628:PRKCA protein, human; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; C058819:calphostin C; D013755:Tetradecanoylphorbol Acetate; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one