Activation of insulin-like growth factor I receptor-mediated pathway by ginsenoside Rg1

Wen Fang Chen, Wai Sum Lau, Pik Yuen Cheung, De An Guo, Man Sau Wong

Research output: Journal article publicationJournal articleAcademic researchpeer-review

36 Citations (Scopus)

Abstract

Ginsenoside Rg1, an active ingredient in ginseng, was previously shown to be a novel class of potent phytoestrogen. The present study aims at investigating the molecular mechanisms involved in mediating its actions in human breast cancer (MCF-7) cells. Rg1 (1 pM) stimulates cell proliferation (P<0.01) and estrogen-responsive pS2 mRNA expression (P<0.05) without alteration of estrogen receptor alpha (ERα) protein or mRNA expression in MCF-7 cells. In addition, 10-14-10-4M of Rg1 does not demonstrate specific binding to ERα. We hypothesize that Rg1 may exert its actions in MCF-7 cell via the activation of crosstalk between ER- and insulin growth factor I receptor (IGF-IR)-dependent pathways. The results indicate that Rg1 significantly increases IGF-IR expression and IGF-IR promoter activity in MCF-7 cells (P<0.05). Cotreatment of MCF-7 cells with 1 μM of estrogen antagonist ICI 182,780 completely abolishes the effects of Rg1 on IGF-IR expression. Furthermore, Rg1 enhances tyrosine phosphorylation of IRS-1 in MCF-7 cells upon IGF-I stimulation and the activation of IRS-1 phosphorylation is also ER-dependent. Taken together, our results suggest that Rg1 not only increases IGF-IR expression but also enhances IGF-IR-mediated signaling pathways in MCF-7 cells. The stimulation of IGF-IR expression by Rg1 in MCF-7 cells appears to require ER, and its actions might involve ligand-independent activation of ER.
Original languageEnglish
Pages (from-to)542-551
Number of pages10
JournalBritish Journal of Pharmacology
Volume147
Issue number5
DOIs
Publication statusPublished - 1 Mar 2006

Keywords

  • Estrogen
  • Ginsenoside Rg1
  • Human breast cancer
  • Insulin-like growth factor I receptor
  • Phytoestrogen

ASJC Scopus subject areas

  • Pharmacology

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