Abstract
Objectives: Long-term hormone replacement therapy is associated with an increased breast cancer
risk. Evidence is accumulating that estradiol metabolites are involved in carcinogenesis.
These metabolites may have proliferating and anti-proliferative properties. We have
investigated the effect of 14 metabolites on the proliferation of human breast cancer
cells and on the proliferation of human vascular endothelial cells. Methods: As cell model, human umbilical vein endothelial cells (HUVEC) and the human breast
cancer cell line MCF-7 were used. The relationship between dosage and effect was tested
over the pharmacological concentration range of 10−8 to 10−5 M. Results: In HUVECs, all of 10 A-ring metabolites tested stimulated the growth of the endothelial
cells at the lower concentrations. At the highest concentration, some A-ring metabolites
caused significant inhibitions. The D-ring metabolites showed no marked effects compared
to the A-ring metabolites. In MCF-7 cells also, nearly all A-ring metabolites demonstrated
a biphasic reaction behaviour on cell proliferation. For the D-ring metabolites, this
biphasic pattern was only found for 16α-hydroxyestrone, but the inhibitory effect
of this metabolite was weak. Conclusion: These results indicate that certain endogenous estradiol metabolites are able to
stimulate breast cancer cell proliferation, and others may be suitable for breast
cancer treatment when used in high dosages, since they inhibit cancer cell growth
as well as neoangiogensis. This may be of special importance for therapy, since some
of these metabolites are virtually devoid of any oestrogenic activity.
Keywords
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Article info
Publication history
Accepted:
February 17,
2004
Received in revised form:
February 3,
2004
Received:
July 23,
2003
Footnotes
☆The data presented have been awarded with the poster prize at the 6th European Congress on Menopause, 24–28 May 2003, Bucharest, Romania. Maturitas 2003; 44 (Suppl. 2): S126 (Poster P01.02).
Identification
Copyright
© 2004 Elsevier Ireland Ltd. Published by Elsevier Inc. All rights reserved.
