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)-1α 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-1α in colon 26 cells, it (10 μM) 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.