Abstract
The Rheum palmatum L., a traditional medicine in Korea, was screened for their estrogenic activity in a recombinant yeast system with a human estrogen receptor (ER) expression plasmid and a reporter plasmid used in a previous study. The EC50 values of the n-hexane, dichloromethane, ethyl acetate, n-butanol, and water fractions of the methanolic extract of R. palmatum in the yeast-based estrogenicity assay system were 0.145, 0.093, 0.125, 1.459, 2.853 µg/mL, respectively, with marked estrogenic activity in the dichloromethane fraction. Using an activity-guided fractionation approach, five known anthraquinones, chrysophanol (1), physcion (2), emodin (3), aloe-emodin (4) and rhein (5), were isolated from the dichloromethane fraction. Compound 3 had the highest estrogenic relative potency (RP, 17bestradiol = 1.00) (6.3 × 10−2), followed by compound 4 (3.8 × 10−3), compound 5 (2.6 × 10−4), a compound 1 (2.1 × 10−4). Also, compound 3 and fraction 3 (which contained compound 3) of the dichloromethane fraction of R. palmatum showed strong cytotoxicity in both ER-positive (MCF-7) and-negative (MDA-MB-231) breast cancer cell lines.
Similar content being viewed by others
References
Adlercreutz, H. and Mazur, W., Phyto-oestrogens and Western diseases. Ann. Med., 29, 95–120 (1997).
Bolton, J. L., Pisha, E., Zhang, F., and Qiu S., Role of quinoids in estrogen carcinogenesis. Chem. Res. Toxicol., 11, 1113–1127 (1998).
Chen, Y. C., Shen, S. C., Lee, W. R., Hsu, F. L., Lin, H. Y., Ko, C. H., and Tseng, S. W., Emodin induces apoptosis in human promyeloleukemic HL-60 cells accompanied by activation of caspase 3 cascade but independent of reactive oxygen species production. Biochem. Pharmacol., 64, 1713–1724 (2002).
Ciocca, D. R. and Roig, L. M., Estrogen receptors in human nontarget tissues: biological and clinical implications. Endocr. Rev., 16, 35–62 (1995).
Colditz, G. A., Hankinson, S. E., Hunter, D. J., Willett, W. C., Manson, J. E., Stampfer, M. J., Hennekens, C., Rosner, B., Speizer, F. E., and Engl, N., The use of estrogens and progestins and the risk of breast cancer in postmenopausal women. J. Med., 332, 1589–1593 (1995).
Eaker, E. D., Chesebro, J. H., Sacks, F. M., Wenger, N. K., Whisnant, J. P., and Winston, M., Cardiovascular disease in women. Circulation, 88, 1999–2009 (1993).
Henderson, B. E., Ross, R., and Bernstein, L., Estrogens as a cause of human cancer: the Richard and Hinda Rosenthal Foundation award lecture. Cancer Res., 48, 246–253 (1988).
Huang, H. C., Chu, S. H., and Chao-lee, P.D., Vasorelaxants from Chinese herbs, emodin and scoparone, possess immuno-suppressive properties. Eur. J. Pharmacol., 198, 211–213 (1991).
Kang, S. C., Lee, C.M., Choi, H., Lee, J.H., Oh, J. S., Kwak, J.H., and Zee, O.P., Evaluation of oriental medicinal herbs for estrogenic and antiproliferative activities. Phythother. Res., 20, 1017–1019 (2006).
Koyama, M., Kelly, T. R., and Watanabe, K. A., Novel type of potential anticancer agents derived from chrysophanol and emodin. J. Med. Chem., 31, 283–284 (1998).
Liang, J. W., Hsiu, S. L., Huang, H. C., and Lee-chao, P.D., HPLC analysis of emodin in serum, herbs and Chinese herbal prescriptions. J. Food Drug Anal., 1, 251–257 (1993).
Liu, R., Li, A., and Sun, A., Preparative isolation and purification of hydroxyanthraquinones and cinnamic acid from the Chinese medicinal herb Rheum officinale Baill. by high-speed counter-current chromatography. J. Chromatography A, 1052, 217–221 (2004).
Palacios, S., Current perspectives on the benefits of HRT in menopausal women. Maturitas, 33(S1), 1–13 (1999).
Rymer, J., Wilson, R., and Ballard, K., Making decisions about hormone replacement therapy. British Medical J., 326, 322–326 (2003).
Skehan, P., Storeng, R., Scudiero, D., Monks, A., McMahon, J., Vistica, D., Warren, J. T., Bokesch, H., Kenney, S., and Boyd, M. R., Comparison of in vitro anticancer-drug-screening data generated with a tetrazolium assay versus a protein assay against a diverse panel of human tumor cell lines. J. Natl. Cancer Inst., 82, 1107–1112 (1990).
Smith, S. S., Female sex steroid hormones: from receptors to networks to performance-actions on the sensorimotor system. Prog. Neurobiol., 44, 55–86 (1994).
Tsai, T. H. and Chen, C. F., Ultraviolet spectrum identification of emodin in rabbit plasma by HPLC and its pharmacokinetics application. Asia Pac. J. Pharmacol., 7, 53–56 (1992).
Woods, H.F., Phytoestrogens and Health. Crown copyright. (2002).
Zhang, L. and Hung, M. C., Sensitization of HER-2/neu-over-expressing non-small cell lung cancer cells to chemotherapeutic drugs by tyrosine kinase inhibitor emodin. Oncogene, 12, 571–576 (1996).
Zhang, L., Lau, Y. K., Xi, L., Hong, R. L., Kim, D. S., Chen, C. F., Hortobagyi, G. N., Chang, C. J., and Hung, M. C., Tyrosine kinase inhibitor, emodin and its derivative repress HER-2/neu-induced cellular transformation and metastasis-associated properties. Oncogene, 16, 2855–2863 (1998).
Zhou, X. M. and Chen, Q. H., Biochemical study of Chinese rhubarb XXII. Inhibitory effect of anthraquinone derivatives on sodium-potassium-ATPase of a rabbit renal medulla and their diuretic action. Acta Pharm. Sin., 23, 17–20 (1998).
Zhou, X., Song, B., Jin, L., Hu, D., Diao, C., Xu, G., Zou, Z., and Yang, S., Isolation and inhibitory activity against ERK Phospohrylation of hydroxyanthraquinones from rhubarb. Bioorg. Med. Chem. Lett., 16, 563–568 (2006).
Author information
Authors and Affiliations
Corresponding authors
Rights and permissions
About this article
Cite this article
Kang, S.C., Lee, C.M., Choung, E.S. et al. Anti-proliferative effects of estrogen receptor-modulating compounds isolated from Rheum palmatum . Arch. Pharm. Res. 31, 722–726 (2008). https://doi.org/10.1007/s12272-001-1218-1
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12272-001-1218-1