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- Title
Ginsenoside Rb1 inhibits tube-like structure formation of endothelial cells by regulating pigment epithelium-derived factor through the oestrogen beta receptor.
- Authors
Leung, K. W.; Cheung, L. W. T.; Pon, Y. L.; Wong, R. N. S.; Mak, N. K.; Fan, T.-Pd; Au, S. C. L.; Tombran-Tink, J.; Wong, A. S. T.; Fan, T-P D
- Abstract
<bold>Background and Purpose: </bold>Angiogenesis is a crucial step in tumour growth and metastasis. Ginsenoside-Rb1 (Rb1), the major active constituent of ginseng, potently inhibits angiogenesis in vivo and in vitro. However, the underlying mechanism remains unknown. We hypothesized that the potent anti-angiogenic protein, pigment epithelium-derived factor (PEDF), is involved in regulating the anti-angiogenic effects of Rb1.<bold>Experimental Approaches: </bold>Rb1-induced PEDF was determined by real-time PCR and western blot analysis. The anti-angiogenic effects of Rb1 were demonstrated using endothelial cell tube formation assay. Competitive ligand-binding and reporter gene assays were employed to indicate the interaction between Rb1 and the oestrogen receptor (ER).<bold>Key Results: </bold>Rb1 significantly increased the transcription, protein expression and secretion of PEDF. Targeted inhibition of PEDF completely prevented Rb1-induced inhibition of endothelial tube formation, suggesting that the anti-angiogenic effect of Rb1 was PEDF specific. Interestingly, the activation of PEDF occurred via a genomic pathway of ERbeta. Competitive ligand-binding assays indicated that Rb1 is a specific agonist of ERbeta, but not ERalpha. Rb1 effectively recruited transcriptional activators and activated an oestrogen-responsive reporter gene. Furthermore, Rb1-mediated PEDF activation and the subsequent inhibition of tube formation were blocked by the ER antagonist ICI 182,780 or transfection of ERbeta siRNA, indicating ERbeta dependence.<bold>Conclusions and Implications: </bold>Here we show for the first time that the Rb1 suppressed the formation of endothelial tube-like structures through modulation of PEDF via ERbeta. These findings demonstrate a novel mechanism of the action of this ginsenoside that may have value in anti-cancer and anti-angiogenesis therapy.
- Subjects
TUMOR growth; METASTASIS; NEOVASCULARIZATION inhibitors; ESTROGEN receptors; BRITISH Journal of Pharmacology (Periodical); PROTEIN metabolism; RNA metabolism; CELL lines; COMPARATIVE studies; EPITHELIAL cells; ESTRADIOL; ESTROGEN antagonists; GLYCOSIDES; RESEARCH methodology; MEDICAL cooperation; NERVE growth factor; PROTEINS; RESEARCH; EVALUATION research; CHEMICAL inhibitors; PHARMACODYNAMICS; CELL physiology
- Publication
British Journal of Pharmacology, 2007, Vol 152, Issue 2, p207
- ISSN
0007-1188
- Publication type
journal article
- DOI
10.1038/sj.bjp.0707359