Relationship between estrogen receptor-binding and estrogenic activities of environmental estrogens and suppression by flavonoids.
In this study, we investigated the estrogenic activity of environmental estrogens by a competition binding assay using a human recombinant estrogens receptor (hERbeta) and by a proliferation assay using MCF-7 cells and a sulforhodamine-B assay. In the binding assay, pharmaceuticals had a stronger binding activity to hERbeta than that of some phytoestrogens (coumestrol, daidzein, genistein, luteolin, chrysin, flavone, and naringenin) or industrial chemicals, but phytoestrogens such as coumestrol had a binding activity as strong as pharmaceuticals such as 17alpha-ethynylestradiol (EE), tamoxifen (Tam), and mestranol. In the proliferation assay, pharmaceuticals such as diethylstilbestrol, EE, Tam, and clomiphene, and industrial chemicals such as 4-nonylphenol, bisphenol A, and 4-dihydroxybiphenyl had a proliferation-stimulating activity as strong as 17beta-estradiol (ES). In addition, we found that phytoestrogens such as coumestrol, daidzein, luteolin, and quercetin exerted a proliferation stimulating activity as strong as ES. Furthermore, we examined the suppression of proliferation-stimulating activity, induced by environmental estrogen, by flavonoids, such as daidzein, genistein, quercetin, and luteolin, and found that these flavonoids suppressed the induction of the proliferation-stimulating activity of environmental estrogens. The suppressive effect of flavonoids suggests that these compounds have anti-estrogenic and anti-cancer activities.
Han
Dal-Ho
DH
Department of Environmental Toxicology, University of California, Davis 95616-8588, USA. dhhan@ucdavis.edu
Denison
Michael S
MS
Tachibana
Hirofumi
H
Yamada
Koji
K
D001667:Binding, Competitive / Q000187:drug effects; D001943:Breast Neoplasms / Q000473:pathology; D002606:Charcoal; D004797:Enzyme-Linked Immunosorbent Assay; D004965:Estrogen Antagonists / Q000494:pharmacology*; D004968:Estrogens, Non-Steroidal / Q000494:pharmacology*; D005260:Female; D005419:Flavonoids / Q000494:pharmacology*; D012739:Gonadal Steroid Hormones / Q000302:isolation & purification; D006801:Humans; D011960:Receptors, Estrogen / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D014407:Tumor Cells, Cultured
D004965:Estrogen Antagonists; D004968:Estrogens, Non-Steroidal; D005419:Flavonoids; D012739:Gonadal Steroid Hormones; D011960:Receptors, Estrogen; D011994:Recombinant Proteins; D002606:Charcoal