In vitro studies of tibolone in breast cells.
OBJECTIVE
To investigate the effects of tibolone and its main metabolites on breast homeostasis.


METHODS
In vitro studies in primary cultures of normal breast cells and in breast cancer cell lines.


METHODS
Hospital-based academic research center.


METHODS
Human breast cells were obtained from women undergoing surgery for hypermastia. Breast cancer cell lines (MCF-7, T47-D, and ZR75-1) were routinely obtained from subcultures.


METHODS
Cells were incubated with tibolone, its various metabolites, the pure pregnane Org 2058, and the androgen dihydrotestosterone.


METHODS
Proliferation was determined by using a morphometric growth index, apoptosis by using morphologic analysis and flow cytometry, and antiapoptotic proteins bcl-2 and bclx(L) by using Western blot assay. Activity of 17beta-hydroxysteroid dehydrogenase was measured as an epithelial differentiation marker.


RESULTS
Tibolone and its delta(4) isomer were antiproliferative in normal breast cells. Tibolone and its delta(4) isomer increased apoptosis in breast cells. These proapoptotic effects were at least partially mediated through decreased expression of the antiapoptotic proteins bcl-2 and bclx(L). An increase in HSD activity was observed after tibolone administration.


CONCLUSIONS
Tibolone is antiproliferative and proapoptotic and induces differentiation in normal breast cells. It is also proapoptotic in breast cancer cell lines.
Gompel
Anne
A
Unite Fonctionnelle de Gynécologie-endocrinienne, Hôpital Hôtel-Dieu AP-HP, Paris, France. anne.gompel@htd.ap-hop-paris.fr
Chaouat
Marc
M
Jacob
Denis
D
Perrot
Jean-Yves
JY
Kloosterboer
Helenius J
HJ
Rostene
William
W
D015067:17-Hydroxysteroid Dehydrogenases / Q000494:pharmacology; D017209:Apoptosis; D001940:Breast / Q000166:cytology*; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D009652:Norpregnenes / Q000378:metabolism / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D009652:Norpregnenes; D015067:17-Hydroxysteroid Dehydrogenases; C044256:3 (or 17)-beta-hydroxysteroid dehydrogenase; C027385:tibolone