title: γ-Tocotrienol reduces human airway smooth muscle cell proliferation and migration.
abstract: OBJECTIVE
  Vitamin E is an antioxidant that occurs in 8 different forms (α, β, γ, and δ tocopherol and tocotrienol). Clinical trials of tocopherol supplementation to assess the impact of antioxidant activity in asthma have yielded equivocal results. Tocotrienol exhibits greater antioxidant activity than tocopherol in several biological phenomena in vivo and in vitro. We tested the effect of tocotrienol on human airway smooth muscle (ASM) cell growth and migration, both of which mediate airway remodeling in asthma.
  
  
  METHODS
  We measured platelet-derived growth factor-BB (PDGF-BB)-induced ASM cell proliferation and migration by colorimetric and Transwell migration assays in the presence and absence of γ-tocotrienol (an isoform of tocotrienol).
  
  
  RESULTS
  PDGF-BB-induced ASM cell proliferation and migration were inhibited by γ-tocotrienol. This effect was associated with inhibition of RhoA activation, but it had no effect on p42/p44 mitogen-activated protein kinase (MAPK) or Akt1 activation. We confirmed that pharmacological inhibition of Rho kinase activity was sufficient to inhibit PDGF-BB-induced ASM cell proliferation and migration.
  
  
  CONCLUSIONS
  γ-Tocotrienol could impart therapeutic benefits for airway remodeling in asthma by inhibiting human ASM cell proliferation and migration.
authors.affiliation: Division of Medical Oncology and Molecular Respirology, Department of Multidisciplinary Internal Medicine, Faculty of Medicine, Tottori University, Yonago, Japan.
authors.forename: Tomoya
authors.initials: T
authors.lastname: Harada
authors.affiliation: Division of Medical Oncology and Molecular Respirology, Department of Multidisciplinary Internal Medicine, Faculty of Medicine, Tottori University, Yonago, Japan. Electronic address: yamasaki@grape.med.tottori-u.ac.jp.
authors.forename: Akira
authors.initials: A
authors.lastname: Yamasaki
authors.affiliation: Division of Medical Oncology and Molecular Respirology, Department of Multidisciplinary Internal Medicine, Faculty of Medicine, Tottori University, Yonago, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Chikumi
authors.affiliation: Division of Medical Oncology and Molecular Respirology, Department of Multidisciplinary Internal Medicine, Faculty of Medicine, Tottori University, Yonago, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Hashimoto
authors.affiliation: Division of Medical Oncology and Molecular Respirology, Department of Multidisciplinary Internal Medicine, Faculty of Medicine, Tottori University, Yonago, Japan.
authors.forename: Ryota
authors.initials: R
authors.lastname: Okazaki
authors.affiliation: Division of Medical Oncology and Molecular Respirology, Department of Multidisciplinary Internal Medicine, Faculty of Medicine, Tottori University, Yonago, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Takata
authors.affiliation: Division of Medical Oncology and Molecular Respirology, Department of Multidisciplinary Internal Medicine, Faculty of Medicine, Tottori University, Yonago, Japan.
authors.forename: Takehito
authors.initials: T
authors.lastname: Fukushima
authors.affiliation: Division of Medical Oncology and Molecular Respirology, Department of Multidisciplinary Internal Medicine, Faculty of Medicine, Tottori University, Yonago, Japan.
authors.forename: Masanari
authors.initials: M
authors.lastname: Watanabe
authors.affiliation: Division of Medical Oncology and Molecular Respirology, Department of Multidisciplinary Internal Medicine, Faculty of Medicine, Tottori University, Yonago, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Kurai
authors.affiliation: Department of Physiology and Internal Medicine, University of Manitoba, Winnipeg, Canada.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Halayko
authors.affiliation: Division of Medical Oncology and Molecular Respirology, Department of Multidisciplinary Internal Medicine, Faculty of Medicine, Tottori University, Yonago, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Shimizu
mesh_terms: D056151:Airway Remodeling / Q000187:drug effects; D000975:Antioxidants / Q000494:pharmacology*; D000077214:Becaplermin; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D002839:Chromans / Q000494:pharmacology*; D003124:Colorimetry; D006801:Humans; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000378:metabolism; D020574:Proto-Oncogene Proteins c-sis / Q000008:administration & dosage; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D002839:Chromans; D020574:Proto-Oncogene Proteins c-sis; D014810:Vitamin E; D000077214:Becaplermin; C013649:plastochromanol 8
keywords: Airway smooth muscle; Asthma; Vitamin E; γ-Tocotrienol