The roots of Angelica keiskei Koizumi (Umbelliferae) have traditionally been used as a health food considered to have
diuretic,
laxative,
analeptic and lactagogue effects. Recently, it has been thought that the roots and herbs of A. keiskei have preventive effects against
coronary heart disease,
hypertension and
cancer. It has been reported that
chalcone derivatives, such as
xanthoangelol and
4-hydroxyderricin, are isolated as main components from this root. Recently, we reported that the 50 %
ethanol extract, the
ethyl acetate-soluble fraction and the isolated
xanthoangelol, inhibited
tumor growth and
metastasis to the lung in
Lewis lung carcinoma (LLC)-bearing mice. In the present study, we examined the effects of
4-hydroxyderricin on
tumor growth and
metastasis to the lung or liver in subcutaneous or intrasplenic LLC-implanted C57BL/6J female mice.
4-Hydroxyderricin at a dose of 50 mg/kg x 2/day orally inhibited the
tumor growth in subcutaneous LLC-implanted mice and inhibited the lung
metastasis and prolonged the survival time in mice after the removal of subcutaneous
tumors by surgical operation.
Doxorubicin (5 mg/kg x 2/week, i. p.) inhibited the
tumor growth and
metastasis to the lung, but it shortened the survival time and reduced the survival rate compared to those in 4-hydroxyderricin-treated mice.
4-Hydroxyderricin inhibited
DNA synthesis in LLC cells at a concentration of 100 microM, but it had no effect on the
DNA synthesis in human umbilical vein endothelial cells (HUVECs) or on the adherence of LLC cells to HUVECs.
4-Hydroxyderricin inhibited
Matrigel-induced formation of capillary-like tubes by HUVECs at concentrations of 10 to 100 microM. The weights of the spleen and thymus in mice with subcutaneously implanted LLC were maintained close to those of normal mice by orally administered
4-hydroxyderricin. In addition,
4-hydroxyderricin (50 mg/kg x 2/day) inhibited the reduction of the numbers of lymphocytes, CD4+, CD8+ and natural killer (NK)-T cells in the spleen of
tumor-removed mice.
Doxorubicin reduced the numbers of lymphocytes, CD4+, CD8+ and NK cells compared to those in LLC-removed mice. These results suggest that the antitumor and antimetastatic activities of
4-hydroxyderricin may be modulated by the immune system and the inhibition of angiogenesis.