Abstract
Ginseng has been recommended to alleviate the menopausal symptoms, which indicates that components of ginseng very likely contain estrogenic activity. We have examined the possibility that a component ofPanax ginseng, ginsenoside-Rb1, acts by binding to estrogen receptor. We have investigated the estrogenic activity of ginsenoside-Rb1, in a transient transfection system using estrogen-responsive luciferase plasmids in MCF-7 cells. Ginsenoside-Rbb1 activated the transcription of the estrogen-responsive luciferase reporter gene in MCF-7 breast cancer cells at a concentration of 50 μM. Activation was inhibited by the specific estrogen receptor antagonist ICI 182,780, indicating that the estrogenic effect of ginsenoside-Rbb1 is estrogen receptor dependent. Next, we evaluated the ability of ginsenoside-Rbb1, to induce the estrogen-responsive gene c-fos by semi-quantitative RT-PCR assays and Western analyses. Ginsenoside-Rbb1 increased c-fos both at mRNA and protein levels. However, ginsenoside-Rbb1 failed to activate the glucocorticoid receptor, the retinoic acid receptor, or the androgen 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-Rbb1 acts a weak phytoestrogen, presumably by binding and activating the estrogen receptor.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Amato, P., Christophe, S., and Mellon, P. L., Estrogenic activity of herbs commonly used as remedies for menopausal symptoms.Menopause, 9, 145–150 (2002).
Attele, A. S., Wu, J. A., and Yuan, C. S., Ginseng pharmacology: Multiple constituents and multiple actions.Biochem. Pharmacol., 58, 1685–1693 (1999).
Bhattaacharya, S. K. and Mitra, S. K., Anxiolytic activity ofpanax ginseng roots: An experimental study.J. Ethnopharmacol., 34, 87–92 (1991).
Chan, R. Y., Chen, W. F., Dong. A., Guo, D., and Wong, M. S., Estrogen-Like Activity of Ginsenoside Rg1 Derived fromPanax notoginseng.J. Clin. Endocrinol. Metabol., 87, 3691–3695 (2002).
Chung, E., Lee, K. Y., Lee, Y. J., Lee, Y. H., and Lee, S. K., Ginsenoside-Rg1 down- regulates glucocorticoid receptor and displays synergistic effects with cAMP.Steroids, 63, 421–424 (1998).
Colditz, G. A., Hormones and breast cancer: evidence and implications for consideration of risks and benefits of hormone replacement therapy.J. Womens Health, 8, 347–357 (1999).
Duda, R. B., Zhong, Y. Z., Navas, V., Li, M. Z. C., Toy, B. R., and Alavarez, J. G., American Ginseng and Breast Cancer Therapeutic Agents Synergistically Inhibit MCF-7 Breast Cancer Cell Growth.J. Surg. Oncol., 72, 230–239 (1999).
Gehm, B. D., McAndrews, J. M., Chien, P. Y., and Jameson, J. L., Resveratrol, a polyphenolic compound found in grapes and wine, is an agonist for the estrogen receptor.Proc. Natl. Acad. Sci., 94, 14138–14143 (1997).
Gehm, B. D., McAndrews, H. M., Jordan, V. C., and Jameson, J. L., EGF activates highly selective estrogen-responsive reporter plasmid by an ER-independent pathway.Mol. Cell Endocrinol., 159, 53–62 (2000).
General information about Korean Red Ginseng website. (http://www.netnam.vn/ic-asia/english/products/redkogin/redkogind/redkogind.htm).
Gillis, C. N.,Panax ginseng Phamacology: A Nitric Oxide Link?Biochem. Pharmacol., 54, 1–8 (1997).
Johnson, S. R., Menopause and hormone replacement therapy.Med. Glin. N. Am., 82, 297–320 (1998).
Kenny, A. M. and Prestwood, K. M., Osteoporosis, Pathogenesis, diagnosis, and treatment in order adults.Rheum. Dis. Clin. North. Am., 26, 569–91 (2000).
Kim, H. S., Zhang, Y. H., Fang, L. H., and Lee, M. K., Effects of ginsenosides on bovine adrenal tyrosine hydroxylase.J. Ethnopharmacol., 66, 107–11 (1999).
Lee, Y. J., Chung, E., Lee, K. W., Lee, Y. H., Huh, B., and Lee, S. K., Ginsenoside-Rg1, one of the major active molecules fromPanax ginseng, is a functional ligand of glucocorticoid receptor.Mol. Cell Endocrinol., 133, 135–140 (1997).
Liu, W. K., Xu, S. X., and Che, C. T., Anti-proliferative effect of ginseng saponins on human prostate cancer cell line.Life Sci., 67, 1297–1306 (2000).
Mercier, G., Turque, N., and Schumacher, M., Rapid Effects of Triiodothyronine on Immediate-Early Gene Expression in Schwann Cells.Glia., 35, 81–89 (2001).
Morschl, E., Bretus, I., Nemcsik, J., Laszlo, F., and Pavo, I., Estrogen-mediated up-regulation of the Ca-dependent constitutive nitric oxide synthase in the rat aorta and heart.Life Sci., 68, 49–55 (2000).
Nah, S. Y. Park, H. J., and McCleskey, E. W., A trace component of ginseng that inhibits Ca2+ channels through a pertussis toxin-sensitive G protein.Proc. Natl. Acad. Sci., 92, 8739–8743 (1995).
Ohminami. H., Kimura, Y., Okuda, H., Tani, T., Arichi, S., and Hayashi, T., Effects of Ginseng Saponins on the Actions of Adrenaline, ACTH and Insulin on Lipolysis and Lipogenesis in Adipose Tissue.Planta. Med., 41, 351–358 (1981).
Paik, N. H., Park, M. K., Choi, K. S., and Cho, Y. H., Isolation of ginsenoside Pb1, Pb2, Rd, Re, Rf and Rg1 from ginseng root by high performance liquid chromatography.Arch. Pharmacol. Res., 5, 7–12 (1982).
Pinkerton, J. V. and Santen, R., Alternative to the Use of Estrogen in Postmenopausal Women.Endocr. Rev., 20, 308–320 (1999).
Ren, L., Marquardt, M. A., and Lech, J. J., Estrogenic effect of nonylphenol on pS2, ER and MUC1 gene expression in human breast cancer cells-MCF-7.Chem. Biol. Interact., 104, 55–64 (1997).
Scott, G. I., Colligan, P. B., Ren, B. H., and Ren, J., Ginsenosides Rb1 and Re Decrease Cardiac Contraction in adult Rat Ventricular Myocytes: Rol of Nitric Oxide.Br. J. Pharmacol., 134, 1159–1165 (2001).
Tyler, V. E., The honest herbal: A sensible guide to the use of herbs and related remedies.New York:Pharmaceutical Products Press. (1993).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Lee, Y.J., Jin, Y.R., Lim, W.C. et al. Ginsenoside-Rb1 acts as a weak phytoestrogen in MCF-7 human breast cancer cells. Arch Pharm Res 26, 58–63 (2003). https://doi.org/10.1007/BF03179933
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF03179933