Cudratricusxanthone A Isolated from the Root Bark of Cudrania tricuspidata Inhibits the Proliferation of Vascular Smooth Muscle Cells through the Suppression of PDGF-Receptor Beta Tyrosine Kinase(Pharmacology)
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概要
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Platelet derived growth factor (PDGF)-BB is one of the most potent vascular smooth muscle cell (VSMC) proliferative factors, and abnormal VSMC proliferation by PDGF-BB plays an important role in the development and progression of cardiovascular problems, including restenosis after coronary angioplasty and atherosclerosis. Previous phytochemical studies on the stems or root barks of Cudrania tricuspidata (Moraceae) resulted in the isolation of various isoprenylated xanthones and flavonoids, some of which have anti-cancer, hepatoprotective, anti-inflammatory and anti-oxidant activities. In the present study, we investigated the antiproliferative effect of cudratricusxanthone A isolated from the root bark of C. tricuspidata and its underlying mechanism in VSMCs. Antiproliferative effects of cudratricusxanthone A on VSMCs were examined by direct cell counting and [^^3H]-thymidine incorporation assays. Cudratricusxanthone A inhibited [^^3H]-thymidine incorporations into DNA in VSMCs that occurred in response to treatment with 50 ng/ml PDGF-BB. PDGF-BB-stimulated DNA synthesis was significantly reduced to 86.1, 80.2, 64.2 and 25.1% at concentrations of 0.1, 1, 2 and 3μM, respectively. Moreover, pre-treatment with cudratricusxanthone A (0.1-3μM) suppressed this PDGF-BB-stimulated cell number in a concentration-dependent manner. The inhibition percentages were 11.1, 22.7, 51.3 and 81.5% at the concentrations of 0.1,1, 2 and 3 μM, respectively. We also investigated the mechanism of antiproliferative effects by cudratricusxanthone A in PDGF-BB-stimulated VSMCs. In Western blot analysis, 50 ng/ml PDGF-BB-stimulated phospholipase C (PLC)γ1, Ras, and extracellular signal-regulated kinasel/2 (ERK1/2) phosphorylations were inhibited by cudratricusxanthone A (0.1-3μM). Consisted with these findings, cudratricusxanthone A inhibited PDGF-receptor β chain (PDGF-Rβ) phosphorylation induced by PDGF-BB in a concentration-dependent manner. These findings suggest that the inhibitory effects of cudratricusxanthone A on DNA synthesis and proliferation by PDGF-BB-stimulated VSMCs are mediated by the suppressions of the PDGF-Rβ and its downstream signaling pathways. Our observation may explain in part mechanistic basis for the prevention of cardiovascular diseases, such as atherosclerosis and restenosis after coronary angioplasty by cudratricusxanthone A.
- 公益社団法人日本薬学会の論文
- 2007-04-01
著者
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Lee Jung-jin
Coll. Of Pharmacy Chungnam National Univ.
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Kim Tack-joong
Div. Of Biological Sci. And Technol. Coll. Of Sci. And Technol. Inst. Of Biomaterials Yonsei Univ.
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Hwang Bang-yeon
韓国
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Hwang Bang-yeon
College Of Pharmacy Research Center For Bioresource And Health Chungbuk National University
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Yun Yeo-pyo
Coll. Of Pharmacy Chungbuk National Univ.
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Yun Yeo-pyo
College Of Pharmacy Research Center For Bioresource And Health Chungbuk National University
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Yoo Hwan-soo
College Of Pharmacy Cbitrc Chungbuk National University
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LEE Kwang-Ho
Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine
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YU Ji-Yeon
College of Pharmacy, Research Center for Bioresource and Health, Chungbuk National University
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Hong Jin
Coll. Of Pharmacy Chungbuk National Univ. Kor
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Hong Jin-tae
College Of Pharmacy Chunghuk National University
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Hwang Ji-hye
College Of Pharmacy Cbitrc Chungbuk National University
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JIN Yong-Ri
Center for Molecular Medicine, Maine Medical Center Research Institute
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JIN Yong-Ri
Research Institute of Veterinary Medicine, CBITRC, Chungbuk National University
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KIM Tack-Joong
Research Center for Bioresource and Health, College of Pharmacy, Chungbuk National University
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HAN Hyeong-Jun
Research Center for Bioresource and Health, College of Pharmacy, Chungbuk National University
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HONG Seong-Su
Research Center for Bioresource and Health, College of Pharmacy, Chungbuk National University
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HWANG Ji-Hye
Research Center for Bioresource and Health, College of Pharmacy, Chungbuk National University
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HWANG Bang-Yeon
Research Center for Bioresource and Health, College of Pharmacy, Chungbuk National University
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YOO Hwan-Soo
Research Center for Bioresource and Health, College of Pharmacy, Chungbuk National University
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LEE Jung-Jin
Research Center for Bioresource and Health, College of Pharmacy, Chungbuk National University
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YU Ji-Yeon
Research Center for Bioresource and Health, College of Pharmacy, Chungbuk National University
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KANG Byoung-Won
Department of Chemistry, Dong-Eui University
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YUN Yeo-Pyo
Research Center for Bioresource and Health, College of Pharmacy, Chungbuk National University
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Kang Byoung-won
Department Of Chemistry Dong-eui University
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Kim Tack-joong
Research Center For Bioresource And Health College Of Pharmacy Chungbuk National University
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Hong Jin
College Of Pharmacy And Cbitrc Chungbuk National University
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Yu Ji-yeon
Inst. For Molecular Biology And Genetics Chonbuk National Univ.
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Hong Seong-su
Research Center For Bioresource And Health College Of Pharmacy Chungbuk National University
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Jin Yong-ri
Center For Molecular Medicine Maine Medical Center Research Institute
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Lee Kwang-ho
Department Of Biotechnology Konkuk University
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Lee Kwang-ho
Department Of Biotechnology College Of Biomedical And Health Science Konkuk University
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Yun Yeo-pyo
Research Center For Bioresource And Health College Of Pharmacy Chungbuk National University
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Yun Yeo-pyo
College Of Pharmacy Cbitrc College Of Pharmacy And Medical Research Center Chungbuk National University
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