Molecular identification of potential selective estrogen receptor modulator (SERM) like properties of phytoestrogens in the human breast cancer cell line MCF-7.
Numerous epidemiologic studies revealed that ethnic populations with higher dietary intake of phytoestrogens have the lowest incidence for breast cancer. The molecular mechanisms which may be responsible for this cancer protective action of phytoestrogens are so far only barely characterised. There are some hints that phytoestrogens may act like selective estrogen receptor modulators (SERMs) on the breast. For this reason we have investigated potential SERM-like properties of the phytoestrogens daidzein (Dai), coumestrol (Cou), and genistein (Gen) in the human breast cancer cell line MCF-7. Effects of these substances on progesterone (PR) and estrogen receptor alpha (ER) mRNA expression and estrogen receptor alpha protein levels were studied in comparison to estradiol (E2) and the synthetic SERMs raloxifene (Ral) and faslodex (ICI 182 780). PR mRNA expression was up-regulated after administration of Cou, whereas treatment with Dai and Gen induced only a faint increase. ER mRNA expression was down-regulated by Cou but not affected by Dai and Gen. The content of ER protein in the breast cancer cells was strongly decreased by Gen, only a faint reduction could be observed following administration of Cou, whereas administration of Dai slightly increases ER protein levels. In summary and in comparison to the effects observed after administration of E2, Ral, and ICI it turned out that Cou shows molecular properties which are very similar to an estrogen receptor agonist like E2, whereas the molecular properties of Gen are comparable to the SERMs ICI and Ral. These results clearly indicate that phytoestrogens differ significantly in regard to their molecular action on breast cancer cells and can be subdivided into distinct functional categories.
Diel
P
P
Institut für Morphologie und Tumorforschung, Deutsche Sporthochschule Köln, Germany.
Olff
S
S
Schmidt
S
S
Michna
H
H
D015153:Blotting, Western; D001940:Breast / Q000166:cytology / Q000187:drug effects; D003375:Coumestrol / Q000737:chemistry / Q000494:pharmacology*; D004032:Diet; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D004968:Estrogens, Non-Steroidal / Q000737:chemistry / Q000494:pharmacology*; D000077267:Fulvestrant; D019833:Genistein / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007529:Isoflavones / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D048789:Phytoestrogens; D028321:Plant Preparations; D012333:RNA, Messenger; D020849:Raloxifene Hydrochloride / Q000494:pharmacology; D011960:Receptors, Estrogen / Q000235:genetics; D011980:Receptors, Progesterone / Q000235:genetics; D020845:Selective Estrogen Receptor Modulators / Q000737:chemistry / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D004965:Estrogen Antagonists; D004968:Estrogens, Non-Steroidal; D007529:Isoflavones; D048789:Phytoestrogens; D028321:Plant Preparations; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D020845:Selective Estrogen Receptor Modulators; D000077267:Fulvestrant; D020849:Raloxifene Hydrochloride; D004958:Estradiol; C004742:daidzein; D019833:Genistein; D003375:Coumestrol