Antiangiogenic activity of 11,11′-dideoxyverticillin, a natural product isolated from the fungus Shiraia bambusicola

The fungus Shiraia bambusicola yields the phytochemical 11,11′-dideoxyverticillin, which has been shown to possess potent anticancer activity both in vitro and in vivo. In this study, we reveal that 11,11′-dideoxyverticillin has anti-angiogenic activities and explore the potential mechanisms for this effect. Treatment with 11,11′-dideoxyverticillin inhibited the proliferation of human umbilical vein endothelial cells (HUVECs) with IC50 values of 0.17 ± 0.05 μM for VEGF-stimulated cells and 0.39 ± 0.08 μM for serum-stimulated cells. 11,11′-Dideoxyverticillin also antagonized the antiapoptotic effects of VEGF on serum-deprived HUVECs, inhibited VEGF-induced HUVEC migration in vitro, and blocked serum-induced HUVEC tube formation. Moreover, 11,11′-dideoxyverticillin completely blocked VEGF-induced microvessel sprouting from Matrigel-embedded rat aortic rings and vessel growth in Matrigel plugs in mice. In addition, 11,11′-dideoxyverticillin decreased VEGF secretion by MDA-MB-468 breast cancer cells, and significantly suppressed VEGF-induced tyrosine phosphorylation of Flt-1 and KDR/Flk-1. This inhibition of receptor phosphorylation was correlated with a marked decrease in VEGF-triggered pERK activation and a dramatic increase in pP38 MAPK, but no apparent change in pAkt. Together, these findings strongly suggest that 11,11′-dideoxyverticillin is a structurally novel angiogenesis inhibitor.