Antiangiogenic activity of 11,11'-dideoxyverticillin, a natural product isolated from the fungus Shiraia bambusicola |
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Authors: | Chen Yi Zhang Yi-Xiang Li Mei-Hong Zhao Wei-Min Shi Yu-Hua Miao Ze-Hong Zhang Xiong-Wen Lin Li-Ping Ding Jian |
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Institution: | Division of Anti-tumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Science, Chinese Academy of Sciences, Shanghai, PR China. |
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Abstract: | 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 IC(50) values of 0.17+/-0.05muM for VEGF-stimulated cells and 0.39+/-0.08muM 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. |
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Keywords: | 11 11′-Dideoxyverticillin HUVEC Angiogenesis VEGF Anticancer |
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