Stimulation of breast cancer cells in vitro by the environmental estrogen enterolactone and the phytoestrogen equol.
The phenolic lignans enterolactone and enterodiol appear periodically in women's urine, dependent upon synthesis from plant-derived lignans by the intestinal microflora. The phytoestrogen equol is also present in women's urine, and is also derived from a vegetarian diet. Antiestrogenic or antiproliferative actions of these compounds have been postulated and related to the observation that there is a reduced incidence of breast cancer associated with diet. We evaluated the estrogenic and antiestrogenic activity of these compounds using four sensitive assays in tissue culture, including the use of human breast cancer cell lines T47D and MCF-7. Unexpectedly, we found that enterolactone and enterodiol, as well as equol, are weak estrogens, and that enterolactone and equol could stimulate the growth of estrogen-dependent breast cancer cell lines. We suggest that these environmental agents can promote the growth of breast cancer, particularly hormone-dependent metastases that may be located near the gut or in the mesenteries or liver, where the concentration of these intestinally produced compounds would be highest. Treatment with an antiestrogen such as tamoxifen blocks the estrogenic activity of these compounds. In the absence of treatment with an antiestrogen such as tamoxifen, hormonal therapy to block steroidal estrogen synthesis in a patient with breast cancer could conceivably be circumvented by a vegeterian diet rich in the precursors to estrogenic compounds such as enterolactone and equol.
Welshons
W V
WV
Department of Human Oncology, University of Wisconsin Clinical Cancer Center Madison 53792.
Murphy
C S
CS
Koch
R
R
Calaf
G
G
Jordan
V C
VC
D015107:4-Butyrolactone / Q000031:analogs & derivatives / Q000494:pharmacology*; D001578:Benzopyrans / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000473:pathology*; D002072:Butylene Glycols / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002839:Chromans / Q000494:pharmacology*; D060754:Equol; D004967:Estrogens; D005260:Female; D005663:Furans / Q000494:pharmacology*; D006801:Humans; D007529:Isoflavones; D017705:Lignans; D011980:Receptors, Progesterone / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects*
C007610:4',7-dihydroxy-3,4-dihydroisoflavone; D001578:Benzopyrans; D002072:Butylene Glycols; D002839:Chromans; D004967:Estrogens; D005663:Furans; D007529:Isoflavones; D017705:Lignans; D011980:Receptors, Progesterone; D060754:Equol; C029498:2,3-bis(3'-hydroxybenzyl)butane-1,4-diol; D015107:4-Butyrolactone; C029497:2,3-bis(3'-hydroxybenzyl)butyrolactone