Studies on Lymphangiogenesis Inhibitors from Korean and Japanese Crude Drugs
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概要
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Metastasis occurs when cancer cells detach from a tumor, travel to distant sites in the body and develop into tumors in these new locations. Most cancer patients die from metastases. Among the various forms of cancer metastasis, lymphatic metastasis is an important determinant in cancer treatment and staging. In this study, we investigated lymphangiogenesis inhibitors from crude drugs used in Japan and Korea. The three crude drugs Saussureae Radix, Psoraleae Semen and Aurantti Fructus Immaturus significantly inhibited the proliferation of temperature-sensitive rat lymphatic endothelial (TR-LE) cells in vitro. By a chromatographic method using bioassay-guided fractionation methods, costunolide (1) and dehydrocostus lactone (2) from S. Radix, p-hydroxybenzaldehyde (3), psoralen (4), angelicin (5), psoracorylifol D (6), isobavachalone (7), bavachinin (8) Δ3,2-hydroxybakuchiol (9) and bakuchiol (10) from P. Semen and cis-octadecyl ferulate (11), (2R)-3β,7,4′-trihydroxy-5-methoxy-8-(γ,γ-dimethylallyl)-flavanone (12), (2S)-7,4′-dihydroxy-5-methoxy-8-(γ,γ-dimethylallyl)-flavanone (13) and umbelliferone (14) from A. F. Immaturus were obtained. Three compounds (compounds 11–13) from A. F. Immaturus were isolated for the first time from this medicinal plant. Among isolated compounds, ten compounds (compounds 1, 2, 6–12, 13) showed an inhibitory effect on the proliferation and the capillary-like tube formation of TR-LE cells. In addition, all compounds except compound 12 showed selective inhibition of the proliferation of TR-LE cells compared to Hela and Lewis lung carcinoma (LLC) cells. These compounds might offer clinical benefits as lymphangiogenesis inhibitors and may be good candidates for novel anti-cancer and anti-metastatic agents.
著者
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WATARI Kousuke
Department of Pharmaceutical Oncology, Graduate School of Pharmaceutical Sciences, Kyushu University
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Kim Youn-chul
College Of Pharmacy Medicinal Resources Research Center Wonkwang University
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Ono Mayumi
Department Of Biochemistry Kyushu University School Of Medicine
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Saiki Ikuo
Division Of Pathogenic Biochemistry Department Of Bioscience Institute Of Natural Medicine Universit
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Koizumi Keiichi
Division Of Pathogenic Biochemistry Department Of Bioscience Institute Of Natural Medicine Universit
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Tanaka Chiaki
Department Of Chemistry Biology And Marine Science And Graduate School Of Engineering And Science Un
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Higuchi Ryuichi
Department of Natural Products Chemistry, Graduate School of Pharmaceutical Sciences, Kyushu University
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Jeong Dami
Department of Natural Products Chemistry, Graduate School of Pharmaceutical Sciences, Kyushu University
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Shirouzu Takayuki
Department of Pharmaceutical Oncology, Graduate School of Pharmaceutical Sciences, Kyushu University
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Miyamoto Tomofumi
Department of Natural Products Chemistry, Graduate School of Pharmaceutical Sciences, Kyushu University
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