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 canc er. The molecular mechanisms which may be responsible for this cancer prote ctive 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 pot ential SERM-like properties of the phytoestrogens daidzein (Dal), coumestro l (Cou), and genistein (Gen) in the human breast cancer cell line MCF-7. Ef fects of these substances on progesterone (PR) and estrogen receptor alpha (ER) mRNA expression and estrogen receptor a 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 administr ation of Cou, whereas treatment with Dal and Gen induced only a faint incre ase. ER mRNA expression was down-regulated by Cou but not affected by Dal a nd Gen. The content of ER protein in the breast cancer cells was strongly d ecreased by Gen, only a faint reduction could be observed following adminis tration of Cou, whereas administration of Dal slightly increases ER protein levels. In summary and in comparison to the effects observed after adminis tration of E2, Rai, and ICI it turned out that Cou shows molecular properti es which are very similar to an estrogen receptor agonist like E2, whereas the molecular properties of Gen are comparable to the SERMs ICI and Rai. Th ese results clearly indicate that phytoestrogens differ significantly in re gard to their molecular action on breast cancer cells and can be subdivided into distinct functional categories.