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

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 (ERalpha) protein or mRNA expression in MCF-7 cells. In addition, 10(-14)-10(-4) M of Rg1 does not demonstrate specific binding to ERalpha. 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 muM 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.

journal_name

Br J Pharmacol

authors

Chen WF,Lau WS,Cheung PY,Guo DA,Wong MS

doi

10.1038/sj.bjp.0706640

subject

Has Abstract

pub_date

2006-03-01 00:00:00

pages

542-51

issue

5

eissn

0007-1188

issn

1476-5381

pii

0706640

journal_volume

147

pub_type

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