3 years ago

H2-P, a honokiol derivative, exerts anti-angiogenesis effects via c-MYC signaling pathway in glioblastoma

Ting Wang, Jialin Wu, Wei Chen
H2-P, a derivative of honokiol , was first synthesized in our laboratory. Compared with honokiol, H2-P has even high anti-tumor activity. In the present study, we evaluated the ability of H2-P to inhibit the survival rate in 4 gliomas cell lines. The result showed that H2-P could significantly inhibit proliferation of gliomas cells in a dose-dependent manner (IC50U251=9.03 nM, IC50SHG-44=10.74 nM, IC50U78=19.87 nM and IC50c6=22.56 nM). Furthermore, to determine the mechanism underlying the anti-gliomas effects of H2-P, 6 kinase activities was detected by Z'-LYTE™ system. The high-throughput screening shown that effect targets of H2-P were MEK and VEGFR2. We also studied the inhibition of H2-P vascular endothelial cells (EA.HY926). The data shown that H2-P could increase endothelial cells apoptosis rate, while inhibiting endothelial cell proliferation (IC5EA.hy926=16.11 nM) and migration. Besides, we investigated anti-angiogenesis of H2-P in the rat thoracic aorta rings, chicken chorioallantoic membrane (CAM) and capillary tube formation models. H2-P showed strong inhibition of angiogenesis. Moreover, we found that H2-P also could reduce tumor volume in mice significantly (P<0.01), and downregulate gene expression level of VEGFR2, MEK and c-MYC in tumor. These data suggest that H2-P have an excellent anti-tumor activity by exerting anti-angiogenesis effects via c-MYC signaling pathway in glioblastoma (GBM). This article is protected by copyright. All rights reserved

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/jcb.26462

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