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Anti-proliferative effects of 1,2-diphenylethane oestrogens and anti-oestrogens on human breast cancer cells

  • Original Papers
  • Experimental Oncology
  • Published:
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Summary

The anti-tumour activities of 1,2-diphenylethane oestrogens (hexoestrol and orthohexoestrol) and anti-oestrogens (metahexoestrol, tetramethylHES, and metatetramethylHES) were studied on the human MCF-7 and MDA-MB-231 breast cancer cell lines. On the E2R-positive MCF-7 cell line, all test compounds exhibited a dose-dependent inhibition of cell proliferation, but no correlation between anti-proliferative activity and binding affinity for the E2R was found. Tested on the E2R-negative MDA-MB-231 cell line, metahexoestrol also showed dose-dependent inhibitory effects, but higher concentrations were necessary than on the MCF-7 cell line. From this it is concluded that the anti-proliferative effect is specific and at least partially mediated via the E2R. Combination of metahexoestrol (10−6M) with E2 (10−9 to 10−7M) gave no rescue effect. It is therefore suggested that this compound might be useful for therapy in the presence of high oestrogen levels, i.e. in pre-menopausal patients. The test compounds (10−8 to 10−6M) could rescue the inhibitory effect of tamoxifen (10−6M) in a dose-dependent manner, except in the cases of metahexoestrol (10−6M) and tetramethylHES (10−6M). The latter compound exhibited a strongly additive effect at this concentration.

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Abbreviations

E2 :

17β-oestradiol

E2R:

oestradiol receptor

DMBA:

9,10-dimethyl-1,2-benzanthracene

NMU:

nitrosomethylurea

IMEM:

improved minimum essential medium

DCC:

dextran coated charcoal

hexoestrol:

meso-3,4-bis(4-hydroxyphenyl)hexane

metahexoestrol:

meso-3,4-bis(3-hydroxyphenyl)hexane

orthohexoestrol:

meso-3,4-bis(2-hydroxyphenyl)hexane

tetramethylHES:

1,1,2,2-tetramethyl-1,2-bis(4-hydroxyphenyl)ethane

metatetramethylHES:

1,1,2,2-tetramethyl-1,2-bis(3-hydroxyphenyl)ethane

C2NCS:

DCC-treated new-born calf serum

EDTA:

ethylenediaminetetraacetic acid

PBS:

phosphate buffered saline

TED:

Tris-EDTA-dithiothreitol

Tris:

tris(hydroxymethyl)aminomethane

TCA:

trichloroacetic acid

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Authors and Affiliations

  1. Institute of Pharmacy, Lehrstuhl Pharmazeutische Chemie II, University of Regensburg, D-8400, Regensburg, Germany

    R. W. Hartmann, T. Sinchai & G. Kranzfelder

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  1. R. W. Hartmann
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  2. T. Sinchai
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  3. G. Kranzfelder
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Dedicated to Prof. Dr. H. Schönenberger on the occasion of his 60th birthday

Supported by grants of the Deutsche Forschungsgemeinschaft (SFB 234-85) and the Verband der Chemischen Industrie, Fonds der Chemischen Industrie

Granted by the Deutscher Akademischer Austauschdienst

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Hartmann, R.W., Sinchai, T. & Kranzfelder, G. Anti-proliferative effects of 1,2-diphenylethane oestrogens and anti-oestrogens on human breast cancer cells. J Cancer Res Clin Oncol 110, 17–24 (1985). https://doi.org/10.1007/BF00402497

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  • DOI: https://doi.org/10.1007/BF00402497

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