Studies on Lymphangiogenesis Inhibitors from Korean and Japanese Crude Drugs

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Author(s)

    • Jeong Dami Jeong Dami
    • Department of Natural Products Chemistry, Graduate School of Pharmaceutical Sciences, Kyushu University
    • Shirouzu Takayuki
    • Department of Pharmaceutical Oncology, Graduate School of Pharmaceutical Sciences, Kyushu University
    • Ono Mayumi
    • Department of Pharmaceutical Oncology, Graduate School of Pharmaceutical Sciences, Kyushu University
    • Koizumi Keiichi
    • Division of Pathogenic Biochemistry, Institute of Natural Medicine, Toyama University
    • Saiki Ikuo
    • Division of Pathogenic Biochemistry, Institute of Natural Medicine, Toyama University
    • Tanaka Chiaki
    • Department of Natural Products Chemistry, Graduate School of Pharmaceutical Sciences, Kyushu University
    • Higuchi Ryuichi
    • Department of Natural Products Chemistry, Graduate School of Pharmaceutical Sciences, Kyushu University

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 <i>in vitro</i>. By a chromatographic method using bioassay-guided fractionation methods, costunolide (<b>1</b>) and dehydrocostus lactone (<b>2</b>) from S. Radix, <i>p</i>-hydroxybenzaldehyde (<b>3</b>), psoralen (<b>4</b>), angelicin (<b>5</b>), psoracorylifol D (<b>6</b>), isobavachalone (<b>7</b>), bavachinin (<b>8</b>) Δ<sup>3</sup>,2-hydroxybakuchiol (<b>9</b>) and bakuchiol (<b>10</b>) from P. Semen and <i>cis</i>-octadecyl ferulate (<b>11</b>), (2<i>R</i>)-3β,7,4′-trihydroxy-5-methoxy-8-(γ,γ-dimethylallyl)-flavanone (<b>12</b>), (2<i>S</i>)-7,4′-dihydroxy-5-methoxy-8-(γ,γ-dimethylallyl)-flavanone (<b>13</b>) and umbelliferone (<b>14</b>) from A. F. Immaturus were obtained. Three compounds (compounds <b>11</b>–<b>13</b>) from A. F. Immaturus were isolated for the first time from this medicinal plant. Among isolated compounds, ten compounds (compounds <b>1</b>, <b>2</b>, <b>6</b>–<b>12</b>, <b>13</b>) showed an inhibitory effect on the proliferation and the capillary-like tube formation of TR-LE cells. In addition, all compounds except compound <b>12</b> 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.

Journal

  • Biological and Pharmaceutical Bulletin

    Biological and Pharmaceutical Bulletin 36(1), 152-157, 2013

    The Pharmaceutical Society of Japan

Codes

  • NII Article ID (NAID)
    130003361357
  • NII NACSIS-CAT ID (NCID)
    AA10885497
  • Text Lang
    ENG
  • ISSN
    0918-6158
  • NDL Article ID
    024173728
  • NDL Call No.
    Z53-V41
  • Data Source
    NDL  J-STAGE 
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