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Combination of quercetin and 2-methoxyestradiol inhibits epithelial–mesenchymal transition in PC-3 cell line via Wnt signaling pathway

    Neeti Sharma

    *Author for correspondence: Tel.: +91 9764435566;

    E-mail Address: neetimohan27@gmail.com

    School of Engineering, Ajeenkya DY Patil University, Charholi Budruk, Pune, 412105, India

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    ,
    Piyush W Raut

    Symbiosis School of Biological Sciences, Symbiosis International (Deemed University), Gram – Lavale; Taluka – Mulshi, Pune, India

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    ,
    Meghna M Baruah

    Symbiosis School of Biological Sciences, Symbiosis International (Deemed University), Gram – Lavale; Taluka – Mulshi, Pune, India

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    &
    Akshay Sharma

    Symbiosis School of Biological Sciences, Symbiosis International (Deemed University), Gram – Lavale; Taluka – Mulshi, Pune, India

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    Published Online:24 Sep 2021https://doi.org/10.2144/fsoa-2021-0028

    Abstract

    Aim: We have previously reported that quercetin (Qu) regulates epithelial–mesenchymal transition (EMT) by modulating Wnt signaling components. In this study, we investigated the synergistic effect of Qu and 2-methoxyestradiol (2-ME) and the role of Wnt signaling components in regulating EMT in PC-3 cells. Materials & methods: EMT was induced by treating PC-3 cells with TGF-β, followed by evaluation of expression of EMT markers and Wnt signaling proteins in naive, induced and after exposing induced cells to Qu and 2-ME at both gene and protein level by real-time PCR (RT-PCR) and western blot, respectively. Results: Qu and 2-ME synergistically downregulated mesenchymal markers with simultaneous upregulation of epithelial markers. Wnt signaling proteins expression was also downregulated by Qu and 2-ME in TGF-β-induced EMT in PC-3 cells. Conclusion: Thus, combination therapy of Qu and 2-ME could be a new promising therapeutic approach for the treatment of prostate cancer.

    Lay abstract

    The current study describes the synergistic effect of quercetin and 2-methoxyestradiol and the role of Wnt signaling components in regulating epithelial–mesenchymal transition (EMT) in PC-3 cells. EMT was induced by treating PC-3 cells with TGF-β, followed by the evaluation of expression of EMT markers and Wnt signaling proteins in naive and induced states. Quercetin and 2-methoxyestradiol could synergistically downregulate mesenchymal markers with simultaneous upregulation of epithelial markers along with the downregulation of Wnt signaling proteins.

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