Effects of letrozole on proliferation and apoptosis in cultured leiomyoma cells treated with prostaglandin E(2)

The objective was to determine the direct effect of letrozole on the proliferation and apoptosis of cultured leiomyoma cells co-treated with prostaglandin E(2) (PGE(2)). Leiomyoma cells were obtained from three groups of patients who had undergone hysterectomy due to leiomyoma. Percentages of antipr...

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Published in:European journal of obstetrics & gynecology and reproductive biology 2008-05, Vol.138 (1), p.83-88
Main Authors: Han, Myoungseok, Kim, Ji Young, Park, Ji-Eun, Kim, Jong-Min, Lee, Kyu-Sup
Format: Article
Language:English
Subjects:
Apoptosis - drug effects
Aromatase Inhibitors - pharmacology
Cell Proliferation - drug effects
Cells, Cultured
Dinoprostone - pharmacology
Enzyme Activators - pharmacology
Female
Humans
Hysterectomy
Leiomyoma - drug therapy
Leiomyoma - pathology
Leiomyoma - surgery
Nitriles - pharmacology
Triazoles - pharmacology
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Summary:The objective was to determine the direct effect of letrozole on the proliferation and apoptosis of cultured leiomyoma cells co-treated with prostaglandin E(2) (PGE(2)). Leiomyoma cells were obtained from three groups of patients who had undergone hysterectomy due to leiomyoma. Percentages of antiproliferative cells were evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and apoptosis was assessed with sub-G1 cell counts by flow cytometry and Western blot analysis. Combined treatment with 100 microM letrozole and 10 microM PGE(2) for 48 h resulted in a significantly lower viability rate (25.9+/-4.5%) and an increased cell death rate (31.6+/-4.4%) than groups treated with letrozole or PGE(2) alone. However, after adding 10nM estradiol to the combined treatment group, the cell viability rate was restored (75.1+/-7.7%) and the cell death rate was decreased (10.5+/-3.1%). Increased caspase-3 expression was found in the letrozole and PGE(2) combined treatment group, but not in the group in which estradiol was added. The present results demonstrate that letrozole inhibits growth and induces apoptosis of leiomyoma cells by blocking the aromatase up-regulated by PGE(2) treatment. These findings support the need for further investigation of aromatase inhibitors as a medical treatment option in leiomyoma.
ISSN:0301-2115
DOI:10.1016/j.ejogrb.2007.05.021