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-Rh1, acts by binding to steroid hormone receptors such as receptors for estrogen, glucocorticoid, androgen, and retinoic acid. Ginsenoside-Rh1 activated the transcription of the estrogen-responsive luciferase reporter gene in MCF-7 breast cancer cells at a concentration of 50 microM. Activation was inhibited by the specific estrogen receptor antagonist ICI 182,780, indicating that the estrogenic effect of ginsenoside-Rh1 is estrogen receptor dependent. Ginsenoside-Rh1 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 24h after treatment, although the effects were not as prominent as 17beta-estradiol. Western blot analysis showed that progesterone receptor protein was induced at 24h of treatment of ginsenoside-Rh1. However, ginsenoside-Rh1 failed to activate the glucocorticoid receptor, the androgen receptor, or the retinoic acid receptor in CV-1 cells transiently transfected with the corresponding steroid hormone receptors and hormone responsive reporter plasmids. These data support our hypothesis that ginsenoside-Rh1 acts as a weak phytoestrogen, presumably by binding and activating the estrogen receptor.
Lee
YoungJoo
Y
Department of Bioscience and Biotechnology, College of Engineering, Institute of Biotechnology, Sejong University, Seoul, South Korea. yjlee@sejong.ac.kr
Jin
YoungRan
Y
Lim
WonChung
W
Ji
SangMi
S
Choi
Songho
S
Jang
Siyoul
S
Lee
SeungKi
S
D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology; D017930:Genes, Reporter; D036145:Ginsenosides / Q000494:pharmacology*; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D008956:Models, Chemical; D010957:Plasmids / Q000378:metabolism; D053766:Presenilin-2; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D011944:Receptors, Androgen / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism*; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014162:Transfection; D014407:Tumor Cells, Cultured
D036145:Ginsenosides; D008565:Membrane Proteins; C508861:PSEN2 protein, human; D053766:Presenilin-2; D016760:Proto-Oncogene Proteins c-fos; D011944:Receptors, Androgen; D011960:Receptors, Estrogen; D018168:Receptors, Retinoic Acid; D004958:Estradiol; C425564:ginsenoside Rh1; D008156:Luciferases