Stimulatory and inhibitory effects of genistein on human uterine leiomyoma cell proliferation are influenced by the concentration

Alicia B. Moore, Lisandra Castro, Linda Chia‐Hui Yu, Xiaolin Zheng, Xudong Di, Maria I. Sifre, Grace E. Kissling, Retha R. Newbold, Carl D. Bortner, Darlene Dixon
In: Human Reproduction · 2007 · vol. 22(10) , pp. 2623–2631 · doi:10.1093/humrep/dem185 · PMID:17725991 · W2170763972
article OA: bronze CC0 ⤵ 7 in-corpus citations
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Genistein at low concentrations stimulates human uterine leiomyoma cell proliferation, while higher concentrations inhibit proliferation and induce apoptosis in both leiomyoma and smooth muscle cells.

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Abstract

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 microg/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 ( or = 10 microg/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.

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