Concentration-dependent effects of a selective estrogen receptor modulator raloxifene on proliferation and apoptosis in human uterine leiomyoma cells cultured in vitro.

Abstract

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 17beta-estradiol (E(2)). 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.

• Authors: Jin Liu, Hiroya Matsuo, Qin Xu, Wei Chen, Jiayin Wang, Takeshi Maruo
• Journal: Human reproduction (Oxford, England) (Hum Reprod) Vol. 22 Issue 5 Pg. 1253-9 (May 2007) ISSN: 0268-1161 [Print] England
• PMID: 17220163 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Proliferating Cell Nuclear Antigen
• Proto-Oncogene Proteins c-bcl-2
• Selective Estrogen Receptor Modulators
• Raloxifene Hydrochloride
• Estradiol

Topics

• Adult
• Apoptosis (drug effects)
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Dose-Response Relationship, Drug
• Estradiol (pharmacology)
• Female
• Humans
• In Situ Nick-End Labeling
• Leiomyoma (physiopathology)
• Middle Aged
• Proliferating Cell Nuclear Antigen (metabolism)
• Proto-Oncogene Proteins c-bcl-2 (biosynthesis)
• Raloxifene Hydrochloride (administration & dosage, pharmacology)
• Selective Estrogen Receptor Modulators (administration & dosage, pharmacology)
• Tumor Cells, Cultured
• Uterine Neoplasms (physiopathology)