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

Heng Yu Chang, Sheng Yi Chen, Chi Hao Wu, Chi Cheng Lu, Gow Chin Yen*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)3323-3332
Number of pages10
JournalJournal of Agricultural and Food Chemistry
Volume67
Issue number12
DOIs
Publication statusPublished - 2019 Mar 27

Keywords

  • E-cadherin
  • EMT
  • glycyrrhizin
  • HMGB1
  • prostate cancer

ASJC Scopus subject areas

  • Chemistry(all)
  • Agricultural and Biological Sciences(all)

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