Gambogic acid inhibits angiogenesis and prostate tumor growth by suppressing vascular endothelial growth factor receptor 2 signaling

被引:228
作者
Yi, Tingfang [1 ]
Yi, Zhengfang [3 ,4 ]
Cho, Sung-Gook [1 ]
Luo, Jian
Pandey, Manoj K. [2 ]
Aggarwal, Bharat B. [2 ]
Liu, Mingyao [1 ,3 ,4 ]
机构
[1] Texas A&M Univ, Syst Hlth Sci Ctr, Ctr Canc & Stem Cell Biol, Inst Biosci & Technol, Houston, TX USA
[2] Univ Texas MD Anderson Canc Ctr, Dept Expt Therapeut, Cytokine Res Lab, Houston, TX USA
[3] E China Normal Univ, Inst Biomed Sci, Shanghai 200062, Peoples R China
[4] Texas A&M Hlth Sci Ctr, Sch Life Sci, Houston, TX 77030 USA
关键词
D O I
10.1158/0008-5472.CAN-07-5944
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Gambogic acid (GA), the main active compound of Gamboge hanburyi, has been previously reported to activate apoptosis in many types of cancer cell lines by targeting transferrin receptor and modulating nuclear factor-kappa B signaling pathway. Whether GA inhibits angiogenesis, which is crucial for cancer and other human diseases, remains unknown. Here, we found that GA significantly inhibited human umbilical vascular endothelial cell (HUVEC) proliferation, migration, invasion, tube formation, and microvessel growth at nanomolar concentration. In a xenograft prostate tumor model, we found that GA effectively inhibited tumor angiogenesis and suppressed tumor growth with low side effects using metronomic chemotherapy with GA. GA was more effective in activating apoptosis and inhibiting proliferation and migration in HUVECs than in human prostate cancer cells (PC3), suggesting GA might be a potential drug candidate in cancer therapy through angioprevention with low chemotoxicity. Furthermore, we showed that GA inhibited the activations of vascular endothelial growth factor receptor 2 and its downstream protein kinases, such as c-Src, focal adhesion kinase, and AKT. Together, these data suggest that GA inhibits angiogenesis and may be a viable drug candidate in antiangiogenesis and anticancer therapies.
引用
收藏
页码:1843 / 1850
页数:8
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