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

Abstract

1 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. 2 Rg1 (1 pM) stimulates cell proliferation (Po0.01) and estrogen-responsive pS2 mRNA expression (Po0.05) without alteration of estrogen receptor alpha (ERa) protein or mRNA expression in MCF-7 cells. In addition, 10 À14 -10 À4 M of Rg1 does not demonstrate specific binding to ERa.3 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. 4 The results indicate that Rg1 significantly increases IGF-IR expression and IGF-IR promoter activity in MCF-7 cells (Po0.05). Cotreatment of MCF-7 cells with 1 mM of estrogen antagonist ICI 182,780 completely abolishes the effects of Rg1 on IGF-IR expression. 5 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. 6 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.

Ginsenoside Rg1 protects against 6-OHDA-induced toxicity in MES23.5 cells via Akt and ERK signaling pathways

“…Ginsenoside Rg1 can stimulate the growth of human breast cancer MCF-7 cells as well as activate estrogen response element-dependent luciferase activities (Chan et al, 2002). Furthermore, we have demonstrated that ginsenoside Rg1 could activate the insulin-like growth factor-I receptor (IGF-IR) signaling pathway through enhancing tyrosine phosphorylation of insulin receptor substrate-1 in MCF-7 cells (Chen et al, 2006). These results suggest that the growth factor signaling pathway is involved in the action of ginsenoside Rg1.…”

Ginsenoside Rg1 promotes bone marrow stromal cells proliferation via the activation of the estrogen receptor-mediated signaling pathway1

“…It has been safely being used in China for more than 2000 years as a tonic against stress. Ginsenosides (steroidal glycosides), in the extracts of various kinds of ginsengs, are the major active components responsible for the pharmacological effects of ginseng on the central nervous, cardiovascular, endocrine, and immune systems [1][2][3][4][5][6] . There are 2 major classes of ginsenosides, protopanaxatriols (Rg1, Rg2, Re, and Rf) and protopanaxadiols (Rb1, Rb2, Rc, and Rd).…”

Extraction-Dependent Effects of American Ginseng (Panax quinquefolium) on Human Breast Cancer Cell Proliferation and Estrogen Receptor Activation

“…21,31 In fact, ginsenoside Rg1 was recently shown to stimulate MCF-7 cell proliferation and pS2 mRNA expression through activation of cross-talk between ER-and insulin growth factor 1 receptor-dependent pathways. 31 Ginsenoside Rb1-induced estrogenic effects in MCF-7 cells also may or may not be mediated by direct interaction with ER. 23,24 The current study addressed the possibility that the extraction method used to extract ginseng will dictate the potential estrogenicity of ginseng products.…”