Hindawi Publishing Corporation Evidence-Based Complementary and Alternative Medicine Volume 2013, Article ID 943187, 10 pages http://dx.doi.org/10.1155/2013/943187 Research Article Butein Inhibits Angiogenesis of Human Endothelial Progenitor Cells via the Translation Dependent Signaling Pathway Ching-Hu Chung, 1 Chien-Hsin Chang, 2 Shiou-Sheng Chen, 3,4 Hsueh-Hsiao Wang, 5 Juei-Yu Yen, 5 Che-Jen Hsiao, 6 Nan-Lin Wu, 7 Yen-Ling Chen, 8 Tur-Fu Huang, 2 Po-Chuan Wang, 9 Hung-I Yeh, 5,10 and Shih-Wei Wang 5 1 Department of Pharmacology, Tzu Chi University, Hualien 970, Taiwan 2 Institute of Pharmacology, College of Medicine, National Taiwan University, Taipei 100, Taiwan 3 Division of Urology, Taipei City Hospital, Renai Branch, Taipei 106, Taiwan 4 Department of Urology, National Yang-Ming University School of Medicine, Taipei 112, Taiwan 5 Department of Medicine, Mackay Medical College, New Taipei City 252, Taiwan 6 School of Respiratory Terapy, College of Medicine, Taipei Medical University, Taipei 110, Taiwan 7 Department of Dermatology, Mackay Memorial Hospital, Hsinchu 300, Taiwan 8 Department of Fragrance and Cosmetic Science, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan 9 Department of Gastroenterology, Mackay Memorial Hospital, Hsinchu 300, Taiwan 10 Department of Internal Medicine, Mackay Memorial Hospital, Taipei 104, Taiwan Correspondence should be addressed to Po-Chuan Wang; a5965@ms7.mmh.org.tw and Shih-Wei Wang; shihwei@mmc.edu.tw Received 27 March 2013; Accepted 9 May 2013 Academic Editor: Shun-Fa Yang Copyright © 2013 Ching-Hu Chung et al. Tis is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 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 efect. 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 efectors, p70S6K, 4E-BP1, and eIF4E in EPCs. Taken together, our results demonstrate for the frst time that butein exhibits the antiangiogenic efect 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. 1. Introduction Angiogenesis plays a critical role in physiological conditions such as embryonic development, reproduction, tissue repair, and bone remodeling. In contrast, angiogenesis is an impor- tant process for tumor progression and various infammatory diseases [1]. Angiogenesis is the result of complex efect on cell-cell and cell-matrix interactions. Tis process mainly involves endothelial cells proliferation, migration, tube for- mation, and extracellular matrix (ECM) degradation [2]. Vascular endothelial growth factor (VEGF) is the most potent angiogenic factor, which is primarily secreted by cancer cells to mediate tumor angiogenesis via binding to VEGF receptor (VEGF-R). Terefore, targeting VEGF/VEGF-R axis to block