Role of G Protein-Coupled Estrogen Receptor in The Regulatory Effects of Phytoestrogens on Prostate Cancer Cell Migration and Invasion.

Abstract

Isoflavones are phytoestrogen compounds that can regulate the growth of prostate cancer (PCa) cells. While most studies indicate phytoestrogens mediate their biological effects by activating estrogen receptors (ERs) ERα and ERβ, recent research suggests that they also activate the G-protein coupled ER (GPER). This study aimed to investigate the effects of genistein and daidzein on cell migration and invasion processes in LNCaP and PC3 human PCa cell lines. Furthermore, the role of GPER as a mediator of the effects of these two isoflavones was evaluated using the specific receptor antagonist G15. LNCaP and PC-3 were pre-treated with G15 (1 μM) before phytoestrogens (50 μM) treatments. Following treatment, cell lines were cultured in Matrigel-uncoated Transwell inserts for migration assays and coated inserts for invasion assays. Treatments with genistein and daidzein significantly decrease cell migration and invasion in LNCaP and PC-3. Additionally, the GPER antagonist G15 suppresses the effects of genistein and daidzein, restoring the migratory and invasive capacities in both cell lines. Based on the results, we suggest that GPER regulates cell migration and invasion of LNCaP and PC-3 mediated by genistein and daidzein. Further research is needed to elucidate the signaling pathways involved to evaluate its role and potential as a therapeutic intervention target in PCa.