OBJECTIVE: 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)). STUDY DESIGN: 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. RESULTS: 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. CONCLUSION: 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.
OBJECTIVE: 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)). STUDY DESIGN: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. RESULTS: 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. CONCLUSION: 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.
Authors: Israel Ortega; Anna Sokalska; Jesus A Villanueva; Amanda B Cress; Donna H Wong; Elisabet Stener-Victorin; Scott D Stanley; Antoni J Duleba Journal: Fertil Steril Date: 2012-11-30 Impact factor: 7.329
Authors: Qiwei Yang; Michal Ciebiera; Maria Victoria Bariani; Mohamed Ali; Hoda Elkafas; Thomas G Boyer; Ayman Al-Hendy Journal: Endocr Rev Date: 2022-07-13 Impact factor: 25.261