The effect of alpha mangostin on epithelial-mesenchymal transition on human hepatocellular carcinoma HepG2 cells surviving sorafenib via TGF-β/smad pathways

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Abstract

Purpose: This study was intended to find out the impact of alpha mangostin administration on the epithelial-mesenchymal transition (EMT) markers and TGF-β/Smad pathways in hepatocellular carcinoma Hep-G2 cells surviving sorafenib. Methods: Hepatocellular carcinoma HepG2 cells were treated with sorafenib 10 μM. Cells surviving sorafenib treatment (HepG2surv) were then treated vehicle, sorafenib, alpha mangostin, or combination of sorafenib and alpha mangostin. Afterward, cells were observed for their morphology with an inverted microscope and counted for cell viability. The concentrations of transforming growth factor (TGF)-β1 in a culture medium were examined using ELISA. The mRNA expressions of TGF-β1, TGF-β1-receptor, Smad3, Smad7, E-cadherin, and vimentin were evaluated using quantitative reverse transcriptase-polymerase chain reaction. The protein level of E-cadherin was also determined using western blot analysis. Results: Treatment of alpha mangostin and sorafenib caused a significant decrease in the viability of sorafenib-surviving HepG2 cells versus control (both groups with P < 0.05). Our study found that alpha mangostin treatment increased the expressions of vimentin (P < 0.001 versus control). In contrast, alpha mangostin treatment tends to decrease the expressions of Smad7 and E-cadherin (both with P > 0.05). In line with our findings, the expressions of TGF-β1 and Smad3 are significantly upregulated after alpha mangostin administration (both with P < 0.05) versus control. Conclusion: Alpha mangostin reduced cell viability of sorafenib-surviving HepG2 cells; however, it also enhanced epithelial-mesenchymal transition markers by activating TGF-β/Smad pathways.

Original languageEnglish
Pages (from-to)648-655
Number of pages8
JournalAdvanced Pharmaceutical Bulletin
Volume10
Issue number4
DOIs
Publication statusPublished - 2020

Keywords

  • Alpha mangostin
  • Epithelial-mesenchymal transition (EMT)
  • Hepatocellular carcinoma
  • Sorafenib
  • TGF-β

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