Hum. Reprod. Advance Access originally published online on January 12, 2007
Human Reproduction 2007 22(5):1253-1259; doi:10.1093/humrep/del515
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Concentration-dependent effects of a selective estrogen receptor modulator raloxifene on proliferation and apoptosis in human uterine leiomyoma cells cultured in vitro
1 Department of Obstetrics and Gynecology 2 Department of Health Sciences, Kobe University Graduate School of Medicine, Kobe, Japan
3 To whom correspondence should be addressed at: Department of Obstetrics and Gynecology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-Cho, Chuo-Ku, Kobe, 650-0017, Japan. Tel: +81 78 382 6000; Fax: +81 78 382 6019; E-mail: maruo{at}kobe-u.ac.jp
BACKGROUND: This study was conducted to elucidate the effects of raloxifene on proliferation and apoptosis in cultured human uterine leiomyoma cells.
METHODS: The monolayer cultures were treated with graded concentrations (10–9, 10–8 and 10–7 M) of raloxifene and 10–7 M 17
-estradiol (E2). Cell viability, percentage of proliferating cell nuclear antigen (PCNA)-positive cells, percentage of terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate nick-end labelling (TUNEL)-positive cells and the expression of PCNA and Bcl-2 proteins were assessed by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxylphenyl)-2-(4-sulphophenyl)-2H-tetraz olium assay, immunocytochemistry, TUNEL assay and western blot analysis, respectively.
RESULTS: Compared with untreated cultures, the number of viable cultured cells, percentage of PCNA-positive cells and PCNA protein expression were significantly decreased by treatment with 10–9 M raloxifene, but increased by treatment with either 10–8 M or 10–7 M raloxifene. In contrast, the percentage of TUNEL-positive cells was significantly increased and Bcl-2 protein expression was significantly decreased by treatment with 10–9 M raloxifene, whereas they were not affected by treatment with either 10–8 or 10–7 M raloxifene.
CONCLUSIONS: In cultured leiomyoma cells, low concentration (10–9 M) of raloxifene may inhibit the growth of leiomyoma cells, whereas high concentrations (10–8 M, 10–7 M) of raloxifene may promote their growth.
Key words: apoptosis/leiomyoma/proliferation/raloxifene/selective estrogen receptor modulator
Submitted on June 30, 2006; resubmitted on November 3, 2006; accepted on December 12, 2006.