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Antitumor and antimetastatic activities of Angelica keiskei roots, part 1: Isolation of an active substance, xanthoangelol.

Abstract

The roots of Angelica keiskei Koizumi have traditionally been used as a health food, with diuretic, laxative, analeptic and galactagogic effects. It has been thought that the roots and leaves of A. keiskei have preventive effects against coronary heart disease, hypertension and cancer. In the present study, we examined the antitumor and antimetastatic activities of various fractions isolated from a 50% ethanol extract of A. keiskei roots. The ethyl acetate-soluble fraction of the 50% ethanol extract inhibited tumor growth in LLC-bearing mice at a daily dose of 100 mg/kg prolonged survival time and inhibited metastasis to the lung after surgical removal of primary tumors. Two active substances were isolated from fractions 1 and 2: compound 1 was identified as xanthoangelol based on the data of the (1)H- and (13)C-NMR spectra. Xanthoangelol inhibited tumor growth in LLC-bearing mice as well as lung metastasis and prolonged survival time in carcinectomized mice at a daily dose of 50 mg per kg. Furthermore, xanthoangelol (50 or 100 mg per kg daily) inhibited liver metastasis and the growth of metastasized tumor cells in the livers of mice with intrasplenically implanted LLC. Xanthoangelol inhibited DNA synthesis in LLC cells at concentrations of 10 and 100 microM, but it had no effect on DNA synthesis in HUVECs or on the adherence of LLC cells to HUVECs. Xanthoangelol inhibited tumor-induced neovascularization (in vivo) at doses of 10 and 20 mg per kg, and it inhibited the Matrigel-induced formation of capillary-like tubes by HUVECs at concentrations of 1-100 microM. Furthermore, xanthoangelol inhibited the binding of VEGF to HUVECs at concentrations of 1-100 microM. These results indicate that the antitumor and/or antimetastatic activities of xanthoangelol may be due to inhibition of DNA synthesis in LLC cells and of tumor-induced neovascularization through inhibition of the formation of capillary-like tubes by vascular endothelial cells and inhibition of the binding of VEGF to vascular endothelial cells.

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  • Authors+Show Affiliations

    ,

    Second Department of Medical Biochemistry, School of Medicine, Ehime University, Shigenobu-cho, Onsen-gun, Ehime 791-0295, Japan. yokim@m.ehime-u.ac.jp

    Source

    MeSH

    Acetates
    Angelica
    Animals
    Antineoplastic Agents
    Carcinoma, Lewis Lung
    Cell Adhesion
    Cell Division
    Chalcone
    DNA Replication
    DNA, Neoplasm
    Endothelial Growth Factors
    Endothelium, Vascular
    Ethanol
    Female
    Fibrinolysin
    Intercellular Signaling Peptides and Proteins
    Liver Neoplasms
    Lung Neoplasms
    Lymphokines
    Mice
    Mice, Inbred C57BL
    Molecular Structure
    Plant Roots
    Survival Rate
    Vascular Endothelial Growth Factor A
    Vascular Endothelial Growth Factors

    Pub Type(s)

    Comparative Study
    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    12845685