Genistein upregulates cyclin D1 and CDK4 expression and promotes the proliferation of ovarian cancer OVCAR-5 cells.

ABSTRACT

BACKGROUND: Ovarian epithelial cancer is the leading cause of deaths associated with gynecologic malignancies. Genistein represents a major type of phytoestrogens widely found in foods and herbal medicines. Although multiple epidemiological studies indicated that the consumption of genistein or other isoflavones is associated with a decreased ovarian cancer risk, the cellular effects and underlying mechanisms are not fully understood. This study focuses on the effect of genistein on the proliferation and cell cycle regulation of ovarian cancer cells. METHODS: Ovarian cancer OVCAR-5 cells were treated with genistein in an estrogen-free condition. Cell counting and MTS assays were performed to determine the cell proliferation alterations. Real-time PCR and Western blotting were conducted to examine the expression changes in key cell cycle regulators. RESULTS: Genistein significantly promoted the proliferation and the viability of OVCAR-5 cells. Upon genistein treatment, cellular mRNA and protein expression levels of PCNA, Cyclin D1 and CDK4 were increased, but those of p21 and p27 were decreased. CONCLUSION: In contrary to results of many previous studies, we observed that genistein was able to upregulate the proliferation and G1-S transition of ovarian cancer OVCAR-5 cells. The discrepancy could be caused by diverged experimental conditions and/or different ER expression patterns of cell lines. The findings may provide basic information for in-depth analysis on the role(s) and mechanisms by which genistein confers its effect on ovarian cancer progression.