Inhibitory effect of PMC, a potent hydrophilic α-tocopherol derivative, on vascular smooth muscle cell proliferation: The pivotal role of PKC-α translocation

Chao Chien Chang, Jie Jen Lee, Cheng-Wen Chiang, Thanasekaran Jayakumar, George Hsiao, Cheng Ying Hsieh, Joen Rong Sheu

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6 Citations (Scopus)

Abstract

Content: 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 α-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. Materials and methods: VSMC proliferation and cytotoxicity were measured by MTT and LDH assays, respectively. The cell cycle and translocation of PKC-α in VSMCs were used by flow cytometry and confocal microscope, respectively. To detect PKC-α 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 50μM)-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)-α translocation and phospho-(Ser/Thr) substrate phosphorylation. Discussion and conclusion: The inhibitory mechanisms of PMC on VSMC proliferation is mediated, at least in part, by inhibition of PKC-α 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.

Original languageEnglish
Pages (from-to)938-946
Number of pages9
JournalPharmaceutical Biology
Volume48
Issue number8
DOIs
Publication statusPublished - Aug 2010

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Keywords

  • α-tocopherol
  • Cell cycle
  • G2/M phase
  • Protein kinase C-α; PMC
  • Vascular smooth muscle cells

ASJC Scopus subject areas

  • Drug Discovery
  • Pharmacology
  • Pharmaceutical Science
  • Complementary and alternative medicine
  • Molecular Medicine

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