Antiestrogenic activities of alternate-substituted polychlorinated dibenzofurans in MCF-7 human breast cancer cells.
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PURPOSE: 1,3,6,8-Substituted alkyl polychlorinated dibenzofurans (PCDFs), typified by 6-methyl-1,3,8-triCDF (MCDF), inhibit 17 beta-estradiol (E2)-induced responses in the rodent uterus and human breast cancer cells. The major purpose of the experiments reported here was to determine the structure-dependent antiestrogenic activities of several alternate-substituted (1,3,6,8- and 2,4,6,8-) PCDFs. METHODS: The antiestrogenic activities were determined in MCF-7 human breast cancer cells using two assays, that is E2-induced cell proliferation and induction of chloramphenicol acetyl transferase (CAT) activity in cells transiently transfected with the E2-responsive Vit-CAT plasmid. RESULTS: MCDF (10(-5) M), 6-isopropyl-1,3,8-triCDF, 6-ethyl-1,3,8-triCDF, 3-isopropyl-6-methyl-1,8-diCDF, and 6-methyl-2,4,8-triCDF, inhibited both E2-induced cell proliferation and CAT activity in MCF-7 cells. All of the remaining ten congeners inhibited either E2-induced cell proliferation or CAT activity, but not both responses. CONCLUSIONS: The antiestrogenic activity of the alternate-substituted PCDFs involves interactions between the aryl hydrocarbon and estrogen receptor signaling pathways. Although these compounds exhibited antiestrogenic activity in MCF-7 cells, the effects of individual congeners were response-specific, and there were no apparent structure-activity relationships.
