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Cell, Tumor, and Stem Cell Biology |
1 Center for Cancer and Stem Cell Biology, Institute for Bioscience and Technology, Texas A&M University System Health Science Center; 2 Cytokine Research Laboratory, Department of Experimental Therapeutics, University of Texas M. D. Anderson Cancer Center, Houston, Texas and 3 Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China
Requests for reprints: Mingyao Liu, Institute of Biosciences and Technology, Texas A&M Health Science Center, 2121 W. Holcombe Boulevard, Houston, TX 77030. Phone: 713-677-7505; Fax: 713-677-7512; E-mail: mliu{at}ibt.tamhsc.edu.
Key Words: gambogic acid antiangiogenesis tumor angiogenesis VEGFR2 inhibitor prostate cancer
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-
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. [Cancer Res 2008;68(6):1843–50]
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Correction: Gambogic Acid Inhibits Angiogenesis and Tumor Growth Cancer Res., May 15, 2008; 68(10): 4012 - 4012. [Full Text] [PDF] |
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