title: Studies on lymphangiogenesis inhibitors from Korean and Japanese crude drugs.
abstract: 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) Δ(3),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.
authors.affiliation: Department of Natural Products Chemistry, Graduate School of Pharmaceutical Sciences, Kyushu University, 3–1–1 Maidashi, Higashi-ku, Fukuoka 812–8582, Japan.
authors.forename: Dami
authors.initials: D
authors.lastname: Jeong
authors.forename: Kousuke
authors.initials: K
authors.lastname: Watari
authors.forename: Takayuki
authors.initials: T
authors.lastname: Shirouzu
authors.forename: Mayumi
authors.initials: M
authors.lastname: Ono
authors.forename: Keiichi
authors.initials: K
authors.lastname: Koizumi
authors.forename: Ikuo
authors.initials: I
authors.lastname: Saiki
authors.forename: Youn-Chul
authors.initials: YC
authors.lastname: Kim
authors.forename: Chiaki
authors.initials: C
authors.lastname: Tanaka
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Higuchi
authors.forename: Tomofumi
authors.initials: T
authors.lastname: Miyamoto
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D005638:Fruit; D006367:HeLa Cells; D006801:Humans; D007564:Japan; D042583:Lymphangiogenesis / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology*; D018517:Plant Roots; D032104:Poncirus; D029907:Psoralea; D051381:Rats; D056910:Republic of Korea; D030441:Saussurea; D012639:Seeds
chemical_list: D020533:Angiogenesis Inhibitors; D010936:Plant Extracts