RRC ID 41911
Author Kimura Y, Baba K.
Title Antitumor and antimetastatic activities of Angelica keiskei roots, part 1: Isolation of an active substance, xanthoangelol.
Journal Int J Cancer
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.
Volume 106(3)
Pages 429-37
Published 2003-9-1
DOI 10.1002/ijc.11256
PMID 12845685
MeSH Acetates / chemistry Angelica / chemistry* Animals Antineoplastic Agents / isolation & purification* Antineoplastic Agents / therapeutic use Carcinoma, Lewis Lung / drug therapy* Carcinoma, Lewis Lung / genetics Carcinoma, Lewis Lung / secondary Cell Adhesion / drug effects Cell Division / drug effects Chalcone / analogs & derivatives* Chalcone / isolation & purification* Chalcone / therapeutic use DNA Replication / drug effects DNA, Neoplasm / drug effects Endothelial Growth Factors / metabolism Endothelium, Vascular / cytology Ethanol / chemistry Female Fibrinolysin / metabolism Intercellular Signaling Peptides and Proteins / metabolism Liver Neoplasms / drug therapy* Liver Neoplasms / genetics Liver Neoplasms / secondary Lung Neoplasms / drug therapy* Lung Neoplasms / genetics Lung Neoplasms / secondary Lymphokines / metabolism Mice Mice, Inbred C57BL Molecular Structure Plant Roots / chemistry* Survival Rate Vascular Endothelial Growth Factor A Vascular Endothelial Growth Factors
IF 5.145
Times Cited 90
Human and Animal Cells