Tibolone and its metabolites inhibit invasion of human mammary carcinoma cells in vitro.
Tibolone is used in postmenopausal women to alleviate menopausal symptoms and to prevent osteoporosis, but it does not stimulate the endometrium and the breast. Up to date, little data are available on the effect of tibolone on breast cancer initiation and progression.


OBJECTIVE
In the present in vitro study, we investigated the effect of tibolone and its metabolites (3alpha-OH tibolone, 3beta-OH tibolone, the Delta4 isomer and the sulphated isoform) on invasion of human breast cancer cells.


METHODS
The effect on invasion was evaluated in the chick heart invasion assay using MCF-7/6 cells and in the collagen type I invasion assay using T47-D cells. Furthermore, the compounds were tested in aggregation and migration assays.


RESULTS
We observed that, at a concentration of 100 microM, tibolone and its 3beta-OH metabolite possess anti-invasive activities in the two different invasion assays. However, this was neither due to effects on cell-cell adhesion nor on motility. In an attempt to probe the mechanism underlying the anti-invasive effect, we found that pro-MMP-9 release was markedly reduced in the supernatant of MCF-7/6 breast cancer cells treated with tibolone, 3alpha-OH tibolone and the Delta4 isomer but, interestingly, not with the sulphated metabolite.


CONCLUSIONS
We conclude that tibolone and its 3beta-OH metabolite have an anti-invasive effect on the tested breast cancer cell lines in vitro. This effect on invasion is not correlated with an effect on cell-cell adhesion or motility but coincides with a decreased release of pro-MMP-9 in the medium.
Vanhoecke
B W
BW
Department of Gynaecology, Ghent University Hospital, De Pintelaan 185, B-9000 Gent, Belgium.
Bracke
M E
ME
Kloosterboer
H J
HJ
Depypere
H T
HT
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D020847:Estrogen Receptor Modulators / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D009361:Neoplasm Invasiveness; D009652:Norpregnenes / Q000494:pharmacology* / Q000627:therapeutic use; D015663:Osteoporosis, Postmenopausal / Q000517:prevention & control
D020847:Estrogen Receptor Modulators; D009652:Norpregnenes; D020780:Matrix Metalloproteinase 9; C027385:tibolone