Inhibitory Effects of BST406, a Newly Synthesized Benzylideneacetophenone Derivative, on Abnormal Vascular Smooth Muscle Cell Proliferation

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概要

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• Benzylideneacetophenone analogues are known to have several significant biological activities, including antiinflammatory, antitumor, antibacterial, antiviral, and gastric-protective activities. However, the antiproliferative effects of benzylideneacetophenone analogues on vascular smooth muscle cells (VSMCs) are unknown. The aim of this study was to elucidate the antiproliferative effects and molecular mechanism of BST406, a newly synthesized benzylideneacetophenone derivative, on platelet-derived growth factor (PDGF)-BB-stimulated rat aortic VSMCs. BST406 inhibited [3H]-thymidine incorporation into DNA in VSMCs following treatment with PDGFBB 25 ng/ml. PDGF-BB-stimulated DNA synthesis was significantly reduced. Moreover, pretreatment with BST406 (0—10μM) suppressed the proliferation of PDGF-BB-stimulated cells in a concentration-dependent manner. We also investigated the mechanism of the antiproliferative effects of BST406 in PDGF-BB-stimulated VSMCs. In Western blot analysis, PDGF-BB-stimulated (25 ng/ml) phospholipase-C (PLC)γ1 and Akt phosphorylation was inhibited by BST406 (0—10μM). However, BST406 did not inhibit the PDGF-receptor β-chain (PDGF-Rβ) and extracellular-regulated kinase 1 and 2 (ERK1/2) phosphorylation induced by PDGF-BB. To confirm that the inhibitory effects of BST406 are mediated through the inhibition of PLCγ1 or Akt, the effects of inhibitors on cell viability were examined. U73122 completely inhibited PDGF-BB-induced proliferation of VSMCs. However, LY294002 10μM had no significant effects on PDGF-BB-induced proliferation. These findings suggest that the inhibitory effects of BST406 on the proliferation of PDGF-BB-stimulated VSMCs are mediated by suppression of the PLCγ1 signaling pathways. Our observations may explain, in part, the mechanistic basis for the prevention of cardiovascular disease (such as atherosclerosis and restenosis after coronary angioplasty) by BST406.

• 日本薬学会の論文

著者

• Kim Tack-Joong

  Division of Biological Science and Technology, College of Science and Technology, Institute of Bioma

• Jung Jae-Chul

  Department of Neuroscience and Medical Research Institute, School of Medicine, Ewha Womans Universit

• Yun Yeo-Pyo

  College of Pharmacy, Chungbuk National University

• Kim Tack-joong

  Div. Of Biological Sci. And Technol. Coll. Of Sci. And Technol. Inst. Of Biomaterials Yonsei Univ.

• Yun Yeo-pyo

  College Of Pharmacy Chungbuk National University

• LEE Jung-Jin

  College of Pharmacy, Research Center for Bioresource and Health, Chungbuk National University

• Han Hyeong-Jun

  College of Pharmacy, Chungbuk National University

• Kim Yong-Jae

  Division of Biological Science and Technology, College of Science and Technology, Yonsei University

• Yu Ji-Yeon

  Institute for Molecular Biology and Genetics, Chonbuk National University

• Yun Yeo-pyo

  College Of Pharmacy Cbitrc College Of Pharmacy And Medical Research Center Chungbuk National Univers

• Kim Tack-joong

  Division Of Biological Science And Technology College Of Science And Technology Yonsei University

• Kim Yong-jae

  Division Of Biological Science And Technology College Of Science And Technology Yonsei University

• Jung Jae-Chul

  Department of Medicinal Chemistry, School of Pharmacy, University of Mississippi

• Lee Jung-Jin

  College of Pharmacy, Chungnam National University

• Yun Yeo-Pyo

  College of Pharmacy and Medical Research Center, Chungbuk National University

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