Formononetin inhibits metastatic potential of human prostate cancer cells via upregulating EGR1

Objectives: Formononetin is a natural isoflavone compound and has been reported to have anti-cancer properties. However, the mechanism by which formononetin inhibits hormone-resistant prostate cancer (PCa) has not been reported. The present study investigates whether and how formononetin inhibits the epithelial-mesenchymal transition (EMT) of hormone-resistant PCa cell lines. Materials and Methods: The proliferation, migration and invasion of PCa cells were analyzed using RTCA system and CCK8 assays. Expression of EMT-related markers and MAPK pathway were analyzed using quantitative reverse transcription PCR (RT-qPCR), immunofluorescence staining and immunoblotting. Gene expression profile was observed by RNA-sequence analysis, and the EGR1 expression analysis in human PCa tissue was referred to the Cancer Genome Atlas database and The Human Atlas Database. Results: Formononetin inhibited the rate of proliferation, migration, and invasion of PCa cells, increased protein levels of E-cadherin, reduced protein levels of fibronectin and the phosphorylated ERK1/2 and JNK, as well as the mRNA levels of the fibronectin, slug and snail. Formononetin remarkably upregulated EGR1, as confirmed by bioinformatics analysis, RT-qPCR and western blotting. Furthermore, the EGR1 expression was lower in human PCa tissue versus its control, and in higher Gleason grade versus the lower Gleason grade PCa. Conclusion: Formononetin could ameliorate tumor aggressiveness via reversing the EMT of hormone-resistant PCa cells. The potential mechanisms involved are inactivation of MAPK signalling and subsequent upregulation of EGR1 expression.