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Glycyrrhizin Attenuates the Process of Epithelial-to-Mesenchymal Transition by Modulating HMGB1 Initiated Novel Signaling Pathway in Prostate Cancer Cells

Chang, Heng-Yu, Chen, Sheng-Yi, Wu, Chi-Hao, Lu, Chi-Cheng, Yen, Gow-Chin
Journal of agricultural and food chemistry 2019 v.67 no.12 pp. 3323-3332
cadherins, cell movement, dose response, gene expression, glycyrrhizin, immunoblotting, metastasis, neoplasm cells, nucleoproteins, patients, prostatic neoplasms, pyruvic acid, signal transduction, therapeutics
High mobility group box 1 (HMGB1) is upregulated in nearly every tumor type. Importantly, clinical evidence also proposed that HMGB1 is particularly increased in metastatic prostate cancer patients. Besides, a growing number of studies highlighted that HMGB1 could be a successful therapeutic target for prostate cancer patients. Glycyrrhizin is a novel pharmacological inhibitor of HMGB1 that may repress prostate cancer metastasis. This research was aimed to investigate the effect of glycyrrhizin on inhibition of HMGB1-induced epithelial-to-mesenchymal transition (EMT), a key step of tumor metastasis, in prostate cancer cells. In this study, HMGB1 knock-downed DU145 prostate cancer cells were used. Silencing the HMGB1 gene expression triggered a change of cell morphology to a more epithelial-like shape, which was accompanied by a reduction of Cdc42/GSK-3β/Snail and induction of E-cadherin levels estimated by immunoblotting. Furthermore, HMGB1 facilitated cell migration and invasion via downstream signaling, whereas HMGB1 targeting by 10 mM ethyl pyruvate effectively inhibited EMT characteristics. Interestingly, cell migration capacity induced by HMGB1 in DU145 cells was abolished in a dose-dependent effect of 25–200 μM glycyrrhizin treatment. In conclusion, glycyrrhizin successfully inhibited HMGB1-induced EMT phenomenon, which suggested that glycyrrhizin may serves as a therapeutic agent for metastatic prostate cancer.