Butein Inhibits Angiogenesis of Human Endothelial Progenitor Cells via the Translation Dependent Signaling Pathway

被引:37
作者
Chung, Ching-Hu [1 ]
Chang, Chien-Hsin [2 ]
Chen, Shiou-Sheng [3 ,4 ]
Wang, Hsueh-Hsiao [5 ]
Yen, Juei-Yu [5 ]
Hsiao, Che-Jen [6 ]
Wu, Nan-Lin [7 ]
Chen, Yen-Ling [8 ]
Huang, Tur-Fu [2 ]
Wang, Po-Chuan [9 ]
Yeh, Hung-I [5 ,10 ]
Wang, Shih-Wei [5 ]
机构
[1] Tzu Chi Univ, Dept Pharmacol, Hualien 970, Taiwan
[2] Natl Taiwan Univ, Inst Pharmacol, Coll Med, Taipei 100, Taiwan
[3] Taipei City Hosp, Div Urol, Renai Branch, Taipei 106, Taiwan
[4] Natl Yang Ming Univ, Dept Urol, Sch Med, Taipei 112, Taiwan
[5] Mackay Med Coll, Dept Med, New Taipei City 252, Taiwan
[6] Taipei Med Univ, Sch Resp Therapy, Coll Med, Taipei 110, Taiwan
[7] Mackay Mem Hosp, Dept Dermatol, Hsinchu 300, Taiwan
[8] Kaohsiung Med Univ, Dept Fragrance & Cosmet Sci, Coll Pharm, Kaohsiung 807, Taiwan
[9] Mackay Mem Hosp, Dept Gastroenterol, Hsinchu 300, Taiwan
[10] Mackay Mem Hosp, Dept Internal Med, Taipei 104, Taiwan
关键词
RAT AORTA; IN-VITRO; MTOR; GROWTH; EXPRESSION; CANCER; PROLIFERATION; APOPTOSIS; BREAST;
D O I
10.1155/2013/943187
中图分类号
R [医药、卫生];
学科分类号
10 ;
摘要
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.
引用
收藏
页数:10
相关论文
共 46 条
[21]   Hypoxia-induced endothelial proliferation requires both mTORC1 and mTORC2 [J].
Li, Weimin ;
Petrimpol, Marco ;
Molle, Klaus D. ;
Hall, Michael N. ;
Battegay, Edouard J. ;
Humar, Rok .
CIRCULATION RESEARCH, 2007, 100 (01) :79-87
[22]   Endothelial p70 S6 kinase 1 in regulating tumor angiogenesis [J].
Liu, Ling-Zhi ;
Zheng, Jenny Z. ;
Wang, Xin-Ru ;
Jiang, Bing-Hua .
CANCER RESEARCH, 2008, 68 (19) :8183-8188
[23]  
Ma FX, 2005, HISTOL HISTOPATHOL, V20, P275, DOI 10.14670/HH-20.275
[24]   MTOR, translation initiation and cancer [J].
Mamane, Y. ;
Petroulakis, E. ;
LeBacquer, O. ;
Sonenberg, N. .
ONCOGENE, 2006, 25 (48) :6416-6422
[25]   Akt-dependent and -independent mechanisms of mTOR regulation in cancer [J].
Memmott, Regan M. ;
Dennis, Phillip A. .
CELLULAR SIGNALLING, 2009, 21 (05) :656-664
[26]   Cap-dependent and cap-independent translation in eukaryotic systems [J].
Merrick, WC .
GENE, 2004, 332 :1-11
[27]   mTOR inhibition induces endothelial progenitor cell death [J].
Miriuka, S. G. ;
Rao, V. ;
Peterson, M. ;
Tumiati, L. ;
Delgado, D. H. ;
Mohan, R. ;
Ramzy, D. ;
Stewart, D. ;
Ross, H. J. ;
Waddell, T. K. .
AMERICAN JOURNAL OF TRANSPLANTATION, 2006, 6 (09) :2069-2079
[28]   Butein induces G2/M phase arrest and apoptosis in human hepatoma cancer cells through ROS generation [J].
Moon, Dong-Oh ;
Kim, Mun-Ock ;
Choi, Yung Hyun ;
Hyun, Jin Won ;
Chang, Weon Young ;
Kim, Gi-Young .
CANCER LETTERS, 2010, 288 (02) :204-213
[29]   Butein suppresses c-Myc-dependent transcription and Akt-dependent phosphorylation of hTERT in human leukemia cells [J].
Moon, Dong-Oh ;
Kim, Mun-Ock ;
Lee, Jae-Dong ;
Choi, Yung Hyun ;
Kim, Gi-Young .
CANCER LETTERS, 2009, 286 (02) :172-179
[30]   Angiogenesis and signal transduction in endothelial cells [J].
Muñoz-Chápuli, R ;
Quesada, AR ;
Medina, MA .
CELLULAR AND MOLECULAR LIFE SCIENCES, 2004, 61 (17) :2224-2243