Genistein inhibits placental choriocarcinoma cell line JAR invasion through ERβ/MTA3/Snail/E-cadherin pathway

Abstract

Abstract. Genistein, the most abundant phytoestrogen in soybeans, may bind to estrogen receptors and perform anticancer activities. Choriocarcinoma is a malignant, trophoblastic and aggressive cancer of the placenta. Few studies are currently available concerning the effects of genistein on choriocarcinoma. In the present study, we investigated the effect of genistein on the invasive potential of the choriocarcinoma cell line JAR and its underlying mechanism. Our data revealed that genistein inhibited JAR cell invasion in a dose-dependent manner by a matrigel invasion assay. Moreover, genistein was found to have decreased the metastasis-associated gene MTA3 mRNA level, increased the transcriptional suppressor Snail mRNA level and upregulated the protein expression of the cell-cell adhesion molecule E-cadherin by real-time RT-PCR and Western blot analysis, respectively. ERβ siRNA was used to knock down ERβ expression in JAR cells. In the ERβ-knockdown JAR cells, genistein failed to inhibit JAR cell invasion. The effects of genistein on MTA3, Snail and E-cadherin expression were also eradicated following ERβ siRNA transfection. These results demonstrated that genistein triggered the MTA3/Snail/E-cadherin regulatory pathway by binding with ERβ, thereby inhibiting JAR cell invasion. In conclusion, our findings have significant implications for the prevention and therapy of choriocarcinoma.

Genistein elicits its anticancer effects through up-regulation of E-Cadherin in Acute Lymphoblastic Leukemia (ALL) cells: an in vitro experimental study

“…Genistein, which is abundantly found in soybean, is anti-proliferative cancer cell. Genistein is a potent inhibitor of tyrosine kinase, which is involved in proliferation signal cascades of cell growth (5), and moderate doses of genistein have been found to have inhibitory effects on prostate, cervix, brain, breast and colon cancers (7). The inhibitory effects of genistein on carcinogenesis and cancer progression have been known for years.…”

“…High correlation was seen between genistein and reduction of the growth rate in time-and dose-dependent manner, higher concentrations of genistein and longer treatment periods demonstrated more reduction in growth rate. Increasing the time of exposure to a higher non-toxic dose of genistein could effectively induce its anti-proliferative effect against acute lymphoblastic leukemia (5). Of course, reduction in growth rate in 72 hours could be due to the lack of nutrients in the cell.…”

“…Genistein is a potent inhibitor of tyrosine kinase, which is involved in proliferation signal cascades of cell growth (5) but with no effect on threonine and serine kinases (6). Moderate doses of genistein have been found to have inhibitory effects on the prostate, cervix, brain, breast, and colon cancers (7).…”

MTA3 regulates CGB5 and Snail genes in trophoblast

“…For example, in cancer cells, MTA3 is directly regulated by estrogen and estrogen receptor alpha (Erα) binding to its promoter [17]. In the trophoblast cell line, JAR, recent research has shown that over-expression of estrogen receptor beta (ERβ) increased MTA3 expression and decreased expression of its target gene, Snail [18]. Furthermore, dys-regulation of estrogen and ERα expression has been reported in preeclamptic placenta [19,20].…”

MTA3 regulates differentiation of human cytotrophoblast stem cells

“…MTA3 is most well-studied in breast cancer, where it has been identified as a key link between estrogen receptor status and tumor invasion [6]. MTA3 has also been implicated in regulation of trophoblast invasion, downstream of estrogen receptor signaling [7]. Expression of MTA3 is also reportedly decreased in preeclampsia [8].…”