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.
Gyeonggi Pharmaceutical Research Center, Suwon, 443-766, Korea.
Se Chan
SC
Kang
Chang Min
CM
Lee
Eui Su
ES
Choung
Jong Phil
JP
Bak
Jong Jin
JJ
Bae
Hyun Sook
HS
Yoo
Jong Hwan
JH
Kwak
Ok Pyo
OP
Zee
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