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

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−14–10−4 M 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.British Journal of Pharmacology (2006) 147, 542–551. doi:10.1038/sj.bjp.0706640; published online 16 January 2006

GINSENG; PHYTOESTROGENS; CELL proliferation; SELECTIVE estrogen receptor modulators; BREAST cancer; ESTROGEN antagonists; MESSENGER RNA

British Journal of Pharmacology, 2006, Vol 147, Issue 5, p542

0007-1188

Academic Journal

10.1038/sj.bjp.0706640