• Yoshiyuki Kimura, Maho Sumiyoshi, and Kimiye Baba.
• 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
• Cancer Lett. 2008 Jun 28; 265 (1): 84-97.

AbstractWe 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.

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