Mitogen-activated protein kinase (MAPK) pathway mediates the oestrogen-like activities of ginsenoside Rg1 in human breast cancer (MCF-7) cells

Br J Pharmacol. 2009 Apr;156(7):1136-46. doi: 10.1111/j.1476-5381.2009.00123.x. Epub 2009 Mar 9.


Background and purpose: The present study was designed to determine how ginsenoside Rg1, an active ingredient in ginseng root, exerts its oestrogenic effects. We hypothesize that Rg1 may exert oestrogen-like actions in MCF-7 cells by activating the mitogen-activated protein kinase (MAPK) pathway in a ligand-independent manner.

Experimental approach: MCF-7 cells were co-incubated with the MAPK inhibitor PD98059 to determine whether the stimulant effects of Rg1 on cell proliferation, the induction of IGF-IR and pS2, the functional transactivation of oestrogen receptor-alpha (ERalpha), as well as ERalpha phosphorylation are dependent on MAPK. The time-dependent responses of mitogen-activated protein kinase kinase (MEK) and extracellular signal-regulated protein kinase (ERK) to Rg1 in MCF-7 cells were studied. The responses of MEK phosphorylation to Rg1 in oestrogen receptor (ER)-negative HEK293 cells were also determined. The effects of Rg1 on cell proliferation and IGF-IR protein expression were studied in the presence of tyrosine kinase inhibitor genistein to elucidate the involvement of tyrosine kinase in mediating these effects.

Key results: The oestrogenic effects of Rg1 in MCF-7 cells were abolished in the presence of PD98059. Rg1 could induce MEK protein expression and the phosphorylation level of MEK and ERK significantly in a time- and dose-dependent manner. Rg1 activated MEK phosphorylation in ER-negative HEK293 cells in a time- and dose-dependent manner. Rg1 induction of cell proliferation and IGF-IR protein expression was abolished by co-treatment with genistein.

Conclusions and implications: Taken together, these results show that the MAPK pathway is involved in mediating the oestrogen-like actions of Rg1 in MCF-7 cells and suggest that Rg1 may activate ERalpha via MEK/ERK in a ligand-independent manner.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms
  • Cell Line
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Enzyme Activation
  • Estrogen Receptor alpha / agonists
  • Estrogen Receptor alpha / metabolism
  • Estrogens / pharmacology*
  • Female
  • Flavonoids / pharmacology
  • Genistein / pharmacology
  • Ginsenosides / pharmacology*
  • Humans
  • MAP Kinase Signaling System / physiology*
  • Mitogen-Activated Protein Kinases / metabolism
  • Phosphorylation
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • Receptor, IGF Type 1 / biosynthesis


  • Estrogen Receptor alpha
  • Estrogens
  • Flavonoids
  • Ginsenosides
  • Genistein
  • Protein-Tyrosine Kinases
  • Receptor, IGF Type 1
  • Mitogen-Activated Protein Kinases
  • ginsenoside Rg1
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one