title: Inhibitory effect of PMC, a potent hydrophilic α-tocopherol derivative, on vascular smooth muscle cell proliferation: the pivotal role of PKC-α translocation.
abstract: BACKGROUND
  Vascular smooth muscle cells (VSMCs) play a major role in the pathogenesis of atherosclerosis and restenosis, and thus the excessive proliferation of VSMCs contributes to neointimal thickening during atherosclerosis and restenosis. PMC (2,2,5,7,8-pentamethyl-6-hydroxychromane) is the most potent hydrophilic derivative of the alpha-tocopherols; it acts as a potent anti-inflammatory and free-radical scavenger.
  
  
  OBJECTIVE
  The present study was designed to examine the inhibitory mechanisms of PMC in VSMC proliferation.
  
  
  METHODS
  VSMC proliferation and cytotoxicity were measured by MTT and LDH assays, respectively. The cell cycle and translocation of PKC-alpha in VSMCs were used by flow cytometry and confocal microscope, respectively. To detect PKC-alpha translocation and activation in VSMCs, immunoblotting was performed in the present study.
  
  
  RESULTS
  In this study, we demonstrate an anti-proliferative effect of PMC in VSMCs. Concentration-dependent inhibition of serum-induced VSMC proliferation was observed in PMC (20 and 50 muM)-treated cells. PMC pretreatment also arrested VSMC cell cycle progression at the G2/M phase. Furthermore, PMC exhibited obvious inhibitory effects on phorbol 12-myristate 13-acetate (PMA)-induced protein kinase C (PKC)-alpha translocation and phospho-(Ser/Thr) substrate phosphorylation.
  
  
  CONCLUSIONS
  The inhibitory mechanisms of PMC on VSMC proliferation is mediated, at least in part, by inhibition of PKC-alpha translocation and causes cell cycle arrest in the G2/M phase. PMC treatment may represent a novel approach for lowering the risk of or improving function in abnormal VSMC proliferation-related vascular diseases.
authors.affiliation: Division of Cardiology, Cathay General Hospital, Taipei.
authors.forename: Chao-Chien
authors.initials: CC
authors.lastname: Chang
authors.forename: Jie-Jen
authors.initials: JJ
authors.lastname: Lee
authors.forename: Cheng-Wen
authors.initials: CW
authors.lastname: Chiang
authors.forename: Thanasekaran
authors.initials: T
authors.lastname: Jayakumar
authors.forename: George
authors.initials: G
authors.lastname: Hsiao
authors.forename: Cheng-Ying
authors.initials: CY
authors.lastname: Hsieh
authors.forename: Joen-Rong
authors.initials: JR
authors.lastname: Sheu
mesh_terms: D000818:Animals; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D002839:Chromans / Q000302:isolation & purification / Q000494:pharmacology*; D016195:G2 Phase / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D051571:Protein Kinase C-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D021381:Protein Transport / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D024502:alpha-Tocopherol / Q000302:isolation & purification / Q000494:pharmacology
chemical_list: D002839:Chromans; C120726:2,2,5,7,8-pentamethyl-6-hydroxychroman; D051571:Protein Kinase C-alpha; D024502:alpha-Tocopherol