Antiestrogenic activities of alternate-substituted polychlorinated dibenzofurans in MCF-7 human breast cancer cells.
OBJECTIVE
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.
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Texas A&M University, College Station 77843-4466, USA.
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D001572:Benzofurans / Q000737:chemistry / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D015500:Chloramphenicol O-Acetyltransferase / Q000096:biosynthesis / Q000187:drug effects; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis / Q000187:drug effects; D000072338:Dibenzofurans, Polychlorinated; D004965:Estrogen Antagonists / Q000494:pharmacology*; D005260:Female; D006801:Humans; D012989:Soil Pollutants / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D001572:Benzofurans; D000072338:Dibenzofurans, Polychlorinated; D004965:Estrogen Antagonists; D012989:Soil Pollutants; D019363:Cytochrome P-450 CYP1A1; D015500:Chloramphenicol O-Acetyltransferase