Effects of tibolone on sulfatase pathway of estrogens metabolism and on growth of MCF-7 human breast tumors implanted in ovariectomized nude mice.
BACKGROUND
The benefits of estrogen plus progestin in healthy post-menopausal women remain uncertain. Tibolone, with its in vitro documented inhibitory effects on estrogens metabolism and its selective action on breast, may be an alternative that could favorably influence the health benefit of hormone replacement therapy.


METHODS
We studied the effect of tibolone on the tumor growth of MCF-7 cells implanted in 40 ovariectomized nude mice, receiving subcutaneous pellets of 17beta-estradiol, estrone, estrone-sulfate or vehicle, and daily gavages of tibolone or placebo.


RESULTS
Tibolone, although used at high dose, did not stimulate nor inhibit the estrogen-induced tumors, nor the tumors in estrogen-deprived mice. Measurements of plasma levels of estrogens indicated that tibolone potently stimulated sulfotransferase activity, but intra-tumor levels of estrogens were not significantly modified by tibolone.


CONCLUSIONS
This in vivo study performed with high dose of orally administered tibolone that allowed its hepatic conversion into active metabolites has shown no significant effect on breast tumors growth. Tibolone increased the circulating sulfated estrogens by its activity on the hepatic sulfation but not the intra-tumor levels of estrogens (free or sulfated). However, further studies of dose-response curve and molecular markers are needed to exclude definitely a stimulatory effect of tibolone on tumor growth.
Desreux
Joëlle
J
Laboratory of Biology of Tumors and Development, Pathology Tower +3, CHU Sart-Tilman, Liège, Belgium.
Kloosterboer
Helenius
H
Noël
Agnès
A
Frankenne
Francis
F
Lemaire
Madeleine
M
Putman
Monique
M
Foidart
Jean-Michel
JM
D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D020847:Estrogen Receptor Modulators / Q000494:pharmacology*; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism / Q000503:physiopathology*; D051379:Mice; D008819:Mice, Nude; D009652:Norpregnenes / Q000494:pharmacology*; D010052:Ovariectomy; D013429:Sulfatases / Q000187:drug effects*; D023041:Xenograft Model Antitumor Assays
D020847:Estrogen Receptor Modulators; D004967:Estrogens; D009652:Norpregnenes; D013429:Sulfatases; C027385:tibolone