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Title: Ginsenoside Rg1 activates ligand-independent estrogenic effects via rapid estrogen receptor signaling pathway
Authors: Gao, QG 
Zhou, LP 
Lee, VHY 
Chan, HY 
Man, CWY 
Wong, MS 
Keywords: Estrogen receptor
Estrogen receptor signaling proteins
Ginsenoside Rg1
G protein-coupled estrogen receptor-1
Mitogen-activated protein kinase
Issue Date: 2019
Publisher: Elsevier
Source: Journal of ginseng research, Oct. 2019, v. 43, no. 4, p. 527-538 How to cite?
Journal: Journal of ginseng research 
Abstract: Background: Ginsenoside Rg1 was shown to exert ligand-independent activation of estrogen receptor (ER) via mitogen-activated protein kinaseemediated pathway. Our study aimed to delineate the mechanisms by which Rg1 activates the rapid ER signaling pathways.
Methods: ER-positive human breast cancer MCF-7 cells and ER-negative human embryonic kidney HEK293 cells were treated with Rg1 (10(-12)M, 10(-8)M), 17 beta-estradiol (10(-8)M), or vehicle. Immunoprecipitation was conducted to investigate the interactions between signaling protein and ER in MCF-7 cells. To determine the roles of these signaling proteins in the actions of Rg1, small interfering RNA or their inhibitors were applied.
Results: Rg1 rapidly induced ERa translocation to plasma membrane via caveolin-1 and the formation of signaling complex involving linker protein (Shc), insulin-like growth factor-I receptor, modulator of nongenomic activity of ER (MNAR), ER alpha, and cellular nonreceptor tyrosine kinase (c-Src) in MCF-7 cells. The induction of extracellular signal-regulated protein kinase and mitogen-activated protein kinase kinase (MEK) phosphorylation in MCF-7 cells by Rg1 was suppressed by cotreatment with small interfering RNA against these signaling proteins. The stimulatory effects of Rg1 on MEK phosphorylation in these cells were suppressed by both PP2 (Src kinase inhibitor) and AG1478 [epidermal growth factor receptor (EGFR) inhibitor]. In addition, Rg1-induced estrogenic activities, EGFR and MEK phosphorylation in MCF-7 cells were abolished by cotreatment with G15 (G protein-coupled estrogen receptor-1 antagonist). The increase in intracellular cyclic AMP accumulation, but not Ca mobilization, in MCF-7 cells by Rg1 could be abolished by G15.
Conclusion: Ginsenoside Rg1 exerted estrogenic actions by rapidly inducing the formation of ER containing signalosome in MCF-7 cells. Additionally, Rg1 could activate EGFR and c-Src ER-independently and exert estrogenic effects via rapid activation of membrane-associated ER and G protein-coupled estrogen receptor.
ISSN: 1226-8453
EISSN: 2093-4947
DOI: 10.1016/j.jgr.2018.03.004
Rights: © 2018 The Korean Society of Ginseng, Published by Elsevier Korea LLC. This is an open access article under the CC BY-NC-NDlicense (
The following publication Gao, Q. G., Zhou, L. P., Lee, V. H. Y., Chan, H. Y., Man, C. W. Y., & Wong, M. S. (2019). Ginsenoside Rg1 activates ligand-independent estrogenic effects via rapid estrogen receptor signaling pathway. Journal of Ginseng Research, 43(4), 527-538 is available at
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