A ginsenoside-Rh1, a component of ginseng saponin, activates estrogen receptor in human breast carcinoma MCF-7 cells

We have examined the possibility that a component of Panax ginseng, ginsenoside-Rh I, acts by binding to steroid hormone receptors such as receptors for estrogen, glucocorticoid, androgen, and retinoic acid. Ginsenoside-Rh I activated the transcription of the estrogen-responsive luciferase reporter gene in MCF-7 breast cancer cells at a concentration of 50 muM. Activation was inhibited by the specific estrogen receptor antagonist ICI 182,780. indicating that the estrogenic effect of ginsenoside-Rh I is estrogen receptor dependent. Ginsenoside-Rh I induction of luciferase activity was dose-dependent in CV-1 cells transiently transfected with estrogen receptor and reporter plasmids. Next, we evaluated the ability of ginsenoside-Rh1 to induce the estrogen-responsive genes in MCF-7 cells. Ginsenoside-Rh1 increased c-fos and pS2 at the mRNA levels at 24 h after treatment, although the effects were not as prominent as 17beta-estradiol. Western blot analysis showed that progesterone receptor protein was induced at 24 h of treatment of ginsenoside-Rh1. However, ginsenoside-Rh I failed to activate the glucocorticoid receptor, the androgen receptor, or the retinoic acid receptor in CV-I cells transiently transfected with the corresponding steroid hormone receptors and hormone responsive reporter plasmids. These data support our hypothesis that ginsenoside-Rh I acts as a weak phytoestrogen, presumably by binding and activating the estrogen receptor. (C) 2003 Elsevier Science Ltd. All rights reserved.