Ginsenoside Rb1 inhibits tube-like structure formation of endothelial cells by regulating pigment epithelium-derived factor through the oestrogen β receptor

K. W. Leung, L. W.T. Cheung, Y. L. Pon, Ricky N S WONG, Nai Ki MAK, T. P.P. Fan, S. C.L. Au, J. Tombran-Tink, A. S.T. Wong*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

88 Citations (Scopus)

Abstract

Background and purpose: 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. Experimental approaches: 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). Key results: 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 ERβ. Competitive ligand-binding assays indicated that Rb1 is a specific agonist of ERβ, but not ERα. 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 ERβ siRNA, indicating ERβ dependence. Conclusions and implications: Here we show for the first time that the Rb1 suppressed the formation of endothelial tube-like structures through modulation of PEDF via ERβ. These findings demonstrate a novel mechanism of the action of this ginsenoside that may have value in anti-cancer and anti-angiogenesis therapy.

Original languageEnglish
Pages (from-to)207-215
Number of pages9
JournalBritish Journal of Pharmacology
Volume152
Issue number2
DOIs
Publication statusPublished - Sep 2007

Scopus Subject Areas

  • Pharmacology

User-Defined Keywords

  • Angiogenesis
  • Endothelial cells
  • Ginseng
  • Oestrogen receptor
  • PEDF

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