Shikonin, Acetylshikonin, and Isobutyroylshikonin Inhibit VEGF-induced Angiogenesis and Suppress Tumor Growth in Lewis Lung Carcinoma-bearing Mice
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概要
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Lithospermum erythrorhizon has been used for treatment of inflammatory diseases and cancer as a folk remedy. Based on the evidences that anti-inflammatory agents frequently exert antiangiogenic activity, thus we examined comparatively the antiangiogenic activities of three naphthoquinone derivatives (shikonin, acetylshikonin, and isobutyroylshikonin) isolated from the plant. Three derivatives exhibited weak cytotoxicity against human umbilical vein endothelial cells (HUVECs) with IC_<50> of over 20μM. Shikonin had more specific inhibitory effects on proliferation and vascular endothelial growth factor (VEGF) production by VEGF compared with different derivatives. All of derivatives significantly suppressed the migration of VEGF treated HUVECs at different optimal concentrations. Also, shikonin and acetylshikonin significantly disrupted VEGF-induced tube formation. Furthermore, three derivatives effectively downregulated the expression of urokinase-type plasminogen activator (uPA), but not its receptor uPAR. Additionally, shikonin significantly inhibited tumor growth in LLC-bearing mice, whereas its derivatives had relatively mild effects. Taken together, our findings suggest that shikonin and its derivatives exhibit the antiangiogenic and antitumorigenic effects by suppressing proliferation and angiogenic factors.
- 社団法人日本薬学会の論文
- 2008-11-01
著者
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Kim Sung-hoon
韓国
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Kim Su-jin
Vestibulocochlear Research Center Of Wonkwang University:college Of Oriental Medicine Kyung Hee Univ
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Lee Eun-ok
Coll. Of Oriental Medicine Kyung Hee Univ.
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Kim Sung‐hoon
韓国
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Kim Su-jin
Division Of Environmental Science And Technology Graduate School Of Agriculture
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Magesh Venkataraman
Cancer Preventive Material Development Research Center College Of Oriental Medicine Kyunghee Univers
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Lee Hong-beom
Division Of Ocean Science Korea Maritime University
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Kim Ji-hyun
Department Of Anatomy Chonbuk National University Medical School:research Center For Allergic Immune
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Kim Ji-young
Graduate School Of Biotechnology And Inst. Of Life Sciences And Resources Kyunghee Univ.
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Ahn K
Korea Research Institute Of Bioscience And Biotechnology
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KIM Sung-Hoon
Toxicology Research Center Korea Research Institute of Chemical Technology
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Ahn K‐s
Cancer Preventive Material Development Research Center College Of Oriental Medicine Kyunghee Univers
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Ahn Kwang
Cancer Preventive Material Dev. Res. Center Coll. Of Oriental Medicine Kyunghee Univ.
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LEE Hyo-Jung
Cancer Preventive Material Development Research Center, College of Oriental Medicine, Kyunghee Unive
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LEE Hyo-Jeong
Cancer Preventive Material Development Research Center, College of Oriental Medicine, Kyunghee Unive
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NAM Dongwoo
Cancer Preventive Material Development Research Center, College of Oriental Medicine, Kyunghee Unive
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LEE Eun-Ok
Cancer Preventive Material Development Research Center, College of Oriental Medicine, Kyunghee Unive
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JUNG Min-Hyung
College of Medicine, Kyunghee University
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AHN Kyoo-Seok
Cancer Preventive Material Development Research Center, College of Oriental Medicine, Kyunghee Unive
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KIM Dae-Keun
College of Pharmacy, Woosuk University
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KIM Sung-Hoon
Cancer Preventive Material Development Research Center, College of Oriental Medicine, Kyunghee Unive
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Jung Min-hyung
College Of Medicine Kyunghee University
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Kim Dae
Coll. Of Pharmacy Woosuk Univ.
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Kim Dae-keun
College Of Pharmacy Woosuk University
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Nam Dongwoo
Cancer Preventive Material Development Research Center College Of Oriental Medicine Kyunghee Univers
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Kim Seung-ae
Cancer Preventive Material Dev. Res. Center Coll. Of Oriental Medicine Kyunghee Univ.
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Lee Hyo-jung
Coll. Of Oriental Medicine Kyung Hee Univ.
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Kim Sung-hoon
Coll. Of Oriental Medicine Kyung Hee Univ.
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Ahn K
Seoul National Univ. Seoul Kor
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Kim Sung-hoon
Cancer Preventive Material Development Research Center College Of Oriental Medicine Kyunghee Univers
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