Effects of tibolone on human breast cancer cells and human vascular coronary cells.
Tibolone is a synthetic progestin with estrogenic and progestogenic properties, used to alleviate menopausal syndromes and for osteoporosis prophylaxis in postmenopausal women. However, only little data are available on tibolone and breast cancer risk and on the effects of tibolone on the cardiovascular system. Therefore, in the present in vitro study, we investigated the effect of tibolone on the growth of the human breast cancer cell line, MCF-7, and on the direct effects of tibolone on the vasculature, i.e. human female coronary endothelial and smooth muscle cells. In the breast cancer cell experiments, tibolone was examined alone and in the presence of 0.1 nM estradiol in the concentration range from 0.001 microM to 1 microM. Tibolone lead to significant cell growth in the concentration range of 0.01 micro M to 1 microM and was not able to inhibit estradiol-induced proliferation at the concentrations of 0.01 microM and 0.1 microM. In the vascular endothelial cell culture experiments, tibolone was tested at the concentrations 0.1 microM, 1 microM and 10 microM. Tibolone reduced the synthesis of endothelin as well as the concentrations of E-selectin, PAI-1 and pro-MMP-1. The magnitude of the effects on these markers varied and was in the range of 11%-42%. Concerning smooth muscle cells, tibolone elicited no changes in the proliferation compared to control values. These data suggest that tibolone does have tumour cell-growth promoting effects in vitro. However, tibolone can positively influence the synthesis of markers in cell cultures of human female coronary artery, which modulate vascular tone and which play a decisive role in the various stages of atherosclerosis. Drawing a clinical consequence from our experiments would result in not recommending the use of tibolone in postmenopausal women at high risk for breast cancer development until long-term controlled clinical studies have been performed on the effect of tibolone administration and breast cancer risk. Experimental studies, such as the present one, are useful to explore mechanisms, but clearly cannot replace clinical studies.
Mueck
A O
AO
Section of Endocrinology and Menopause, Department of Obstetrics and Gynecology, University of Tuebingen, Schleichstrasse 4, 72076 Tuebingen, Germany. endo.meno@med.uni-tuebingen.de
Lippert
C
C
Seeger
H
H
Wallwiener
D
D
D001943:Breast Neoplasms / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D003331:Coronary Vessels / Q000166:cytology*; D019040:E-Selectin / Q000032:analysis; D016232:Endothelins / Q000032:analysis; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D004958:Estradiol / Q000008:administration & dosage; D005260:Female; D006801:Humans; D020781:Matrix Metalloproteinase 1 / Q000032:analysis; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009652:Norpregnenes / Q000494:pharmacology*; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis; D014407:Tumor Cells, Cultured
D019040:E-Selectin; D016232:Endothelins; D009652:Norpregnenes; D017395:Plasminogen Activator Inhibitor 1; D004958:Estradiol; D020781:Matrix Metalloproteinase 1; C027385:tibolone