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H2‐P, a honokiol derivative, exerts anti‐angiogenesis effects via c‐MYC signaling pathway in glioblastoma
Author(s) -
Wang Ting,
Chen Wei,
Wu Jialin
Publication year - 2018
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.26462
Subject(s) - angiogenesis , honokiol , apoptosis , cancer research , chorioallantoic membrane , chemistry , signal transduction , downregulation and upregulation , endothelial stem cell , glioblastoma , biology , medicine , pharmacology , in vitro , gene , biochemistry
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 four gliomas cell lines. The result showed that H2‐P could significantly inhibit proliferation of gliomas cells in a dose‐dependent manner (IC50 U251 = 9.03, IC50 SHG‐44 = 10.74, IC50 U78 = 19.87, and IC50 c6 = 22.56 nM). Furthermore, to determine the mechanism underlying the anti‐gliomas effects of H2‐P, six 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 (IC50 EA.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).