INFLUENCE OF VALPROATE AND PHENYTOIN ON ESTROGEN STIMULATED CELL GROWTH IN THE HUMAN BREAST CANCER CELL LINE MCF-7.
Abstract number :
2.268
Submission category :
Year :
2002
Submission ID :
1446
Source :
www.aesnet.org
Presentation date :
12/7/2002 12:00:00 AM
Published date :
Dec 1, 2002, 06:00 AM
Authors :
Line S. Roste, Christel M. Olsen, Elise T.M. Meussen-Elholm, Erik Tauboll. Department of Neurology, Rikshospitalet, University of Oslo, Oslo, Norway; Division of Environmental Medicine, Norwegian Institute of Public Health, Oslo, Norway
RATIONALE: Disturbances in the estrogen pathway seen in women with epilepsy are, at least in part, induced by antiepileptic drugs. Valproate (VPA) induces hyperandrogenism, while phenytoin (PHT) reduces estrogen and progesterone levels. The sites of action of these disturbances are still not completely known. If this can be related to an antiestrogen effect similar to the effects of antiestrogenic substances used in cancer therapy, this would be an important clinical observation. The aim of the study was therefore to evaluate if VPA or PHT reduced estrogen-stimulated cell growth in the estrogen-dependent human breast cancer cell-line MCF-7.
METHODS: MCF-7 cells were grown in phenolred-free Dulbecco[ssquote]s modified Eagle[ssquote]s medium supplemented with 10% charcoal-dextran treated foetal bovine serum. Cell growth was measured as [mu]g DNA after 6 days of co-exposure to 30 pM 17[beta]-estradiol and VPA or PHT at different concentrations. The findings were compared to cell growth in cultures without drug.
RESULTS: PTH 100 [mu]M reduced estrogen stimulated cell growth with 55%. VPA reduced cell growth by 47% and 62% at 250 and 500 [mu]M, respectively. No increased cell-death or reduced metabolism was observed after 24 hours exposure of MCF-7 cells to 500 [mu]M VPA.
CONCLUSIONS: VPA and PHT decrease cell growth in the human breast cancer cell line MCF-7 at clinically relevant serum concentrations. This opens new therapeutic perspectives in the treatment of patients with estrogen sensitive tumors and the findings should be explored further.