TY - JOUR
T1 - Studies on lymphangiogenesis inhibitors from Korean and Japanese crude drugs
AU - Jeong, Dami
AU - Watari, Kousuke
AU - Shirouzu, Takayuki
AU - Ono, Mayumi
AU - Koizumi, Keiichi
AU - Saiki, Ikuo
AU - Kim, Youn Chul
AU - Tanaka, Chiaki
AU - Higuchi, Ryuichi
AU - Miyamoto, Tomofumi
PY - 2013/1
Y1 - 2013/1
N2 - 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.
AB - 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.
KW - Aurantti fructus immaturus
KW - Bakuchiol
KW - Costunolide
KW - Lymphangiogenesis
KW - Psoraleae semen
KW - Saussureae radix
UR - http://www.scopus.com/inward/record.url?scp=84872742625&partnerID=8YFLogxK
U2 - 10.1248/bpb.b12-00871
DO - 10.1248/bpb.b12-00871
M3 - 学術論文
C2 - 23302649
AN - SCOPUS:84872742625
SN - 0918-6158
VL - 36
SP - 152
EP - 157
JO - Biological and Pharmaceutical Bulletin
JF - Biological and Pharmaceutical Bulletin
IS - 1
ER -