Anti-proliferative effects of estrogen receptor-modulating compounds isolated from Rheum palmatum.
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 microg/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 x 10(-2)), followed by compound 4 (3.8 x 10(-3)), compound 5 (2.6 x 10(-4)), a compound 1 (2.1 x 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.
Kang
Se Chan
SC
Gyeonggi Pharmaceutical Research Center, Suwon, 443-766, Korea.
Lee
Chang Min
CM
Choung
Eui Su
ES
Bak
Jong Phil
JP
Bae
Jong Jin
JJ
Yoo
Hyun Sook
HS
Kwak
Jong Hwan
JH
Zee
Ok Pyo
OP
D000880:Anthraquinones / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004642:Emodin / Q000031:analogs & derivatives / Q000494:pharmacology; D020847:Estrogen Receptor Modulators / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D018517:Plant Roots; D011960:Receptors, Estrogen / Q000187:drug effects* / Q000235:genetics; D011994:Recombinant Proteins / Q000187:drug effects; D012250:Rheum / Q000737:chemistry
D000880:Anthraquinones; D000972:Antineoplastic Agents, Phytogenic; D020847:Estrogen Receptor Modulators; D011960:Receptors, Estrogen; D011994:Recombinant Proteins; C518327:aloe emodin; C008905:physcione; D004642:Emodin; C027113:chrysophanic acid; C020491:rhein