Inhibitory effect of statins on the proliferation of human breast cancer cells.
OBJECTIVE
Long-term hormone therapy in the postmenopause is associated with a moderate increase in cardiovascular and breast cancer risk. Of great concern, therefore, is the question of how women with menopausal symptoms and enhanced cardiovascular risk can be treated. Evidence is growing that an estrogen/statin combination may be a good choice, since this combination seems to elicit additive beneficial effects on the lipid profile and on the vasculature.


METHODS
In the present study, the effect of two statins on the proliferation of breast cancer cells in the presence and absence of estradiol was investigated.


RESULTS
Atorvastatin and fluvastatin were able to inhibit the proliferation of MCF-7 cells in the absence of estradiol. This effect seems to depend on an apoptotic statin effect which may be mediated by the down-regulation of the anti-apoptotic protein Bcl-2 rather than up-regulation of Fas-L or p53. However, in the presence of estradiol the inhibitory effect of the statins was less pronounced.


CONCLUSIONS
The present data indicate that statins may possess anticancerogenic properties concerning the development of breast cancer in postmenopausal women. Clinical trials are necessary to prove a beneficial statin effect on breast cancer risk when combined with long-term hormone therapy.
Mück
A O
AO
Section of Endocrinology and Menopause, University Women's Hospital, Tübingen, Germany. endo.meno@med.uni-tuebingen.de
Seeger
H
H
Wallwiener
D
D
D000924:Anticholesteremic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D000069059:Atorvastatin; D001943:Breast Neoplasms; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004336:Drug Antagonism; D004958:Estradiol / Q000009:adverse effects; D004967:Estrogens / Q000009:adverse effects; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology*; D005260:Female; D000077340:Fluvastatin; D006538:Heptanoic Acids / Q000494:pharmacology*; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D009376:Neoplasms, Hormone-Dependent; D011758:Pyrroles / Q000494:pharmacology*
D000924:Anticholesteremic Agents; D004967:Estrogens; D005229:Fatty Acids, Monounsaturated; D006538:Heptanoic Acids; D007211:Indoles; D011758:Pyrroles; D000077340:Fluvastatin; D004958:Estradiol; D000069059:Atorvastatin