Hum. Reprod. Advance Access originally published online on August 27, 2007
Human Reproduction 2007 22(10):2623-2631; doi:10.1093/humrep/dem185
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Stimulatory and inhibitory effects of genistein on human uterine leiomyoma cell proliferation are influenced by the concentration
1 Comparative Pathobiology Group, Laboratory of Experimental Pathology, National Institute of Environmental Health Sciences, National Institutes of Health (NIH), Department of Health and Human Services (DHHS), Research Triangle Park, NC 27709, USA 2 Molecular Endocrinology Group, Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, NIH, DHHS, Research Triangle Park, NC 27709, USA 3 Biostatistics Branch, National Institute of Environmental Health Sciences, NIH, DHHS, Research Triangle Park, NC 27709, USA 4 Developmental Endocrinology and Endocrine Disruptor Section, Laboratory of Molecular Toxicology, National Institute of Environmental Health Sciences, NIH, DHHS, Research Triangle Park, NC 27709, USA
5 Correspondence address. Tel: +1-919-541-3814; Fax: +1-919-541-0637; E-mail: dixon{at}niehs.nih.gov
BACKGROUND: Due to dietary exposure of women to genistein, a soy-derived phytoestrogen, and the estrogen responsiveness of uterine leiomyomas ‘fibroids’, we evaluated the effects of genistein (0.001–50 µg/ml) on human uterine leiomyoma (UtLM) cells versus uterine smooth muscle cells (UtSMCs) in vitro.
METHODS: Light microscopy was used to determine the effects of genistein on cell morphology. Proliferation was assessed using a colorimetric assay and proliferating cell nuclear antigen (PCNA) immunocytochemistry. Flow cytometry was used to quantitate cells in the S-phase and those undergoing apoptosis. A fluorometric assay and confocal microscopy were used to detect caspase-3 activity and apoptotic bodies, respectively.
RESULTS: In UtLM cells, low concentrations (
1 µg/ml) of genistein stimulated proliferation, increased PCNA labeling and the percentage of cells in the S-phase, but this did not occur in UtSMCs. Higher concentrations (
10 µg/ml) of genistein adversely affected the morphology, significantly inhibited proliferation, decreased PCNA labeling, increased caspase-3 activity and induced apoptosis in both cell types.
CONCLUSIONS: Genistein’s effects are concentration-dependent in both cell lines. Lower concentrations elicit proliferative effects on UtLM cells only; whereas, higher concentrations alter morphology, inhibit proliferation, and increase caspase activity and apoptosis in both cell types, with the latter two effects being more extensive in UtSMCs.
Key words: apoptosis/cell proliferation/genistein/uterine leiomyoma (UtLM) cells/uterine smooth muscle cells (UtSMCs)
Submitted on March 14, 2007; resubmitted on May 22, 2007; accepted on May 29, 2007.
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