Document Detail

Estrogenic tamoxifen derivatives: categorization of intrinsic estrogenicity in MCF-7 cells.
MedLine Citation:
PMID:  9459186     Owner:  NLM     Status:  MEDLINE    
Triarylethylenes bearing acetic acid side chains, exemplified by 4-[1-(p-hydroxyphenyl)-2-phenyl-1-butenyl]phenoxyacetic acid (4HTA), a derivative of tamoxifen (TAM), are of current interest as estrogen mimics lacking reproductive tract effects. Affinities for estrogen receptors (ER) and effects on cell growth kinetics of a diverse series of such compounds were compared with 4HTA, TAM, and with standard estrogens 17beta-estradiol (E2) and chlorotrianisene (CTA) in MCF-7 cells. These compounds exhibited concentration dependent cell growth stimulation comparable to that of CTA but less than that of E2. Growth stimulation of the more potent compounds was antagonized by TAM, signifying that effects were mediated via interaction with ER. At concentrations of 1 microM or higher, compounds with efficacies less than that of E2 were weak antagonists of estradiol-stimulated growth. Both intracellular ER affinities and growth rate stimulation potencies of the triarylethylene acetic acids and the standard ER ligands varied over a range of nearly three orders of magnitude. Analysis of growth stimulatory potency as a function of ER affinity revealed dual parallel correlations: the potency/ER affinity ratios of 4HTA and four of its analogues was about 100-fold less than those of the hydroxytriarylethane and bisphenolic analogs and the three standard ER ligands. These results suggested that ER liganded with the latter substances is more 'effective' at nuclear effector sites than is ER liganded with 4HTA and the other acidic triarylethylenes.
P C Ruenitz; S A Moore; K S Kraft; C S Bourne
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of steroid biochemistry and molecular biology     Volume:  63     ISSN:  0960-0760     ISO Abbreviation:  J. Steroid Biochem. Mol. Biol.     Publication Date:    1997 Nov-Dec
Date Detail:
Created Date:  1998-02-18     Completed Date:  1998-02-18     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  9015483     Medline TA:  J Steroid Biochem Mol Biol     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  203-9     Citation Subset:  IM    
College of Pharmacy, University of Georgia, Athens 30602-2352, USA.
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MeSH Terms
Breast Neoplasms / metabolism*,  pathology
Cell Division / drug effects
Cell Line
Estrogens / metabolism*
Molecular Mimicry
Protein Binding
Receptors, Estrogen / metabolism
Tamoxifen / analogs & derivatives*,  pharmacology
Tumor Cells, Cultured
Grant Support
Reg. No./Substance:
0/Estrogens; 0/Receptors, Estrogen; 10540-29-1/Tamoxifen

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