Department of Pharmacology, Tzu Chi University, Hualien 970, Taiwan.
Evid Based Complement Alternat Med. 2013;2013:943187. doi: 10.1155/2013/943187. Epub 2013 Jun 6.
Compelling evidence indicates that bone marrow-derived endothelial progenitor cells (EPCs) can contribute to postnatal neovascularization and tumor angiogenesis. EPCs have been shown to play a "catalytic" role in metastatic progression by mediating the angiogenic switch. Understanding the pharmacological functions and molecular targets of natural products is critical for drug development. Butein, a natural chalcone derivative, has been reported to exert potent anticancer activity. However, the antiangiogenic activity of butein has not been addressed. In this study, we found that butein inhibited serum- and vascular endothelial growth factor- (VEGF-) induced cell proliferation, migration, and tube formation of human EPCs in a concentration dependent manner without cytotoxic effect. Furthermore, butein markedly abrogated VEGF-induced vessels sprouting from aortic rings and suppressed microvessel formation in the Matrigel implant assay in vivo. In addition, butein concentration-dependently repressed the phosphorylation of Akt, mTOR, and the major downstream effectors, p70S6K, 4E-BP1, and eIF4E in EPCs. Taken together, our results demonstrate for the first time that butein exhibits the antiangiogenic effect both in vitro and in vivo by targeting the translational machinery. Butein is a promising angiogenesis inhibitor with the potential for treatment of cancer and other angiogenesis-related diseases.
有确凿的证据表明，骨髓来源的内皮祖细胞（EPCs）可以促进出生后新生血管形成和肿瘤血管生成。已经证明 EPCs 通过介导血管生成开关在转移进展中发挥“催化”作用。了解天然产物的药理功能和分子靶点对于药物开发至关重要。白杨素是一种天然查尔酮衍生物，已被报道具有很强的抗癌活性。然而，白杨素的抗血管生成活性尚未得到解决。在这项研究中，我们发现白杨素以浓度依赖的方式抑制了血清和血管内皮生长因子（VEGF）诱导的人 EPC 细胞增殖、迁移和管状形成，而没有细胞毒性作用。此外，白杨素显著阻断了 VEGF 诱导的主动脉环中血管芽生，并抑制了体内 Matrigel 植入试验中的微血管形成。此外，白杨素浓度依赖性地抑制了 EPC 中 Akt、mTOR 及其主要下游效应物 p70S6K、4E-BP1 和 eIF4E 的磷酸化。总之，我们的结果首次表明，白杨素通过靶向翻译机制在体内和体外均表现出抗血管生成作用。白杨素是一种很有前途的血管生成抑制剂，有望用于治疗癌症和其他与血管生成相关的疾病。
