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    Formononetin Inhibits Metastatic Potential of Human Prostate Cancer Cells via Upregulating EGR1

    Xue Liang2,3, Ziquan Lan2,4, Yiqiao Huang2, Ganggang Jiang2,5, Ting Liu2,3 Corresponding author

    1. 1Key Laboratory of Biological Targeting Diagnosis, Therapy and Rehabilitation of Guangdong Higher Education Institutes, The Fifth Affiliated Hospital of Guangzhou Medical University, China.
    2. 2Guangzhou Key Laboratory of Enhanced Recovery after Abdominal Surgery, The Fifth Affiliated Hospital of Guangzhou Medical University, China.
    3. 3Guangzhou Hosipital of Integrated Traditional and West Medicine, Guangzhou, China.
    4. 4Department of Urological Surgery, The Third Affiliated Hospital of Shenzhen University, Shenzhen, China.

    CORRESPONDENCE

    Ting Liu

    Guangzhou Key Laboratory of Enhanced Recovery after Abdominal Surgery, The Fifth Affiliated Hospital of Guangzhou Medical University, China.

    liuting1985@gzhmu.edu

    Received: 06-07-2021; Revised: 24-03-2022; Accepted: 27-04-2022.

    Volume 18, Issue 80 · pp. 932–939 · PUBLISHED 23 November 2022 · DOI: 10.4103/pm.pm_296_21

    View on Pharmacogn. Mag. original site ↗

    ABSTRACT

    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.

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      Liang, X., Lan, Z., Huang, Y., Jiang, G., & Liu, T. (2022). Formononetin Inhibits Metastatic Potential of Human Prostate Cancer Cells via Upregulating EGR1. Pharmacognosy Magazine, 18(80), 932–939. https://doi.org/10.4103/pm.pm_296_21