Anti-tumor actions of major component 3'-O-acetylhamaudol of Angelica japonica roots through dual actions, anti-angiogenesis and intestinal intraepithelial lymphocyte activation.
We recently demonstrated that two chalcones isolated from Angelica keiskei roots have anti-tumor and anti-metastatic activities through the inhibition of tumor-induced angiogenesis, but the anti-tumor substances of Angelica japonica roots are unknown. We attempted to clarify the anti-tumor action and its mechanisms of a major component 3'-O-acetylhamaudol isolated from A. japonica roots. We first examined the effects of 3'-O-acetylhamaudol on tumor growth in colon 26-bearing mice. Furthermore, we examined the effects of 3'-O-acetylhamaudol on angiogenic factors (vascular endothelial growth factor receptor-2 (VEGFR-2) phosphorylation in human umbilical vein endothelial cells (HUVECs), and vascular endothelial growth factor (VEGF) production and hypoxia-inducible factor (HIF)-1alpha expression in tumors). 3'-O-Acetylhamaudol (25 and 50 mg/kg, twice daily) inhibited the tumor growth in colon 26-bearing mice. Although 3'-O-acetylhamudol had no effect on the VEGF production and HIF-1alpha in colon 26 cells, it (10 microM) inhibited the VEGF-induced angiogenesis and VEGF-induced VEGFR-2 phosphorylation in HUVECs. 3'-O-Acetylhamaudol has anti-tumor effects mediated through dual mechanisms, i.e., anti-angiogenic actions and the modulation of the immune system in the spleen and small intestine in tumor-bearing mice.
Kimura
Yoshiyuki
Y
Division of Biochemical Pharmacology, Department of Basic Medical Research Graduate School of Medicine, Ehime University, Shitsukawa, Toon City, Ehime 791-0295, Japan. yokim@m.ehime-u.ac.jp
Sumiyoshi
Maho
M
Baba
Kimiye
K
D029969:Angelica / Q000737:chemistry*; D020533:Angiogenesis Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology* / Q000627:therapeutic use; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology* / Q000627:therapeutic use; D003110:Colonic Neoplasms / Q000098:blood supply / Q000188:drug therapy / Q000473:pathology; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology; D005110:Extracellular Space / Q000378:metabolism; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D007413:Intestinal Mucosa / Q000276:immunology / Q000473:pathology*; D007421:Intestine, Small / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D010766:Phosphorylation; D018517:Plant Roots / Q000737:chemistry*; D014183:Transplantation, Heterologous; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
C531008:3'-O-acetylhamaudol; D020533:Angiogenesis Inhibitors; D000972:Antineoplastic Agents, Phytogenic; D002867:Chromones; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D040301:Vascular Endothelial Growth Factor Receptor-2