Antiestrogenic activities of alternate-substituted polychlorinated dibenzofurans in MCF-7 human breast cancer cells |
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Authors: | Gulan Sun S Safe |
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Institution: | (1) Veterinary Physiology and Pharmacology, Texas A&M University, College Station, TX 77843-4466, USA Tel 409-845-5988; Fax 409-862-4929, US |
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Abstract: | Purpose: 1,3,6,8-Substituted alkyl polychlorinated dibenzofurans (PCDFs), typified by 6-methyl-1,3,8-triCDF (MCDF), inhibit 17β-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.
Received: 26 July 1996 / Accepted: 16 November 1996 |
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Keywords: | Alternate-substituted PCDFs Antiestrogens |
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