1. Gekko-sulfated glycopeptide inhibits tumor angiogenesis by targeting basic fibroblast growth factor.
- Author
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Zhang SX, Zhu C, Ba Y, Chen D, Zhou XL, Cao R, Wang LP, Ren Y, and Wu XZ
- Subjects
- Animals, Carcinoma, Hepatocellular blood supply, Carcinoma, Hepatocellular metabolism, Chick Embryo, Chickens, Drug Discovery, Drugs, Chinese Herbal metabolism, Early Growth Response Protein 1 genetics, Early Growth Response Protein 1 metabolism, Glucuronidase metabolism, Hep G2 Cells, Heparin metabolism, Human Umbilical Vein Endothelial Cells, Humans, Liver Neoplasms, Experimental blood supply, Liver Neoplasms, Experimental metabolism, Male, Mice, Mice, Nude, Neovascularization, Pathologic metabolism, Polysaccharides metabolism, Surface Plasmon Resonance, Xenograft Model Antitumor Assays, Carcinoma, Hepatocellular drug therapy, Drugs, Chinese Herbal pharmacology, Fibroblast Growth Factor 2 metabolism, Liver Neoplasms, Experimental drug therapy, Neovascularization, Pathologic drug therapy, Polysaccharides pharmacology
- Abstract
Basic fibroblast growth factor (bFGF) is a therapeutic target of anti-angiogenesis. Here, we report that a novel sulfated glycopeptide derived from Gekko swinhonis Guenther (GSPP), an anticancer drug in traditional Chinese medicine, inhibits tumor angiogenesis by targeting bFGF. GSPP significantly decreased the production of bFGF in hepatoma cells by suppressing early growth response-1. GSPP inhibited the release of bFGF from extracellular matrix by blocking heparanase enzymatic activity. Moreover, GSPP competitively inhibited bFGF binding to heparin/heparan sulfate via direct binding to bFGF. Importantly, GSPP abrogated the bFGF-stimulated proliferation and migration of endothelial cells, whereas it had no inhibitory effect on endothelial cells in the absence of bFGF. Further study revealed that GSPP prevented bFGF-induced neovascularization and inhibited tumor angiogenesis and tumor growth in a xenograft mouse model. These results demonstrate that GSPP inhibits tumor angiogenesis by blocking bFGF production, release from the extracellular matrix, and binding to its low affinity receptor, heparin/heparan sulfate.
- Published
- 2012
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