Wheatgrass extract inhibits hypoxia-inducible factor-1-mediated epithelial-mesenchymal transition in A549 cells

  • Do, Nam Yong (Department of Otorhinolaryngology-Head & Neck Surgery, Chosun University College of Medicine) ;
  • Shin, Hyun-Jae (Department of Biochemical and Polymer Engineering, Chosun University) ;
  • Lee, Ji-Eun (Department of Otorhinolaryngology-Head & Neck Surgery, Chosun University College of Medicine)
  • Received : 2016.09.06
  • Accepted : 2016.11.22
  • Published : 2017.04.01


BACKGROUND/OBJECTIVES: Epithelial-mesenchymal transition (EMT) is involved in not only cancer development and metastasis but also non-cancerous conditions. Hypoxia is one of the proposed critical factors contributing to formation of chronic rhinosinusitis or nasal polyposis. Wheatgrass (Triticum aestivum) has antioxidant, anti-aging, and anti-inflammatory effects. In this study, we analyzed whether wheatgrass has an inhibitory effect on the EMT process in airway epithelial cells. MATERIALS/METHODS: A549 human lung adenocarcinoma cells were incubated in hypoxic conditions ($CO_2$ 5%/$O_2$ 1%) for 24 h in the presence of different concentrations of wheatgrass extract (50, 75, 100, and $150{\mu}g/mL$) and changes in expression of epithelial or mesenchymal markers were evaluated by immunoblotting and immunofluorescence. Accordingly, associated EMT-related transcriptional factors, Snail and Smad, were also evaluated. RESULTS: Hypoxia increased expression of N-cadherin and reduced expression of E-cadherin. Mechanistically, E-cadherin levels were recovered during hypoxia by silencing hypoxia inducible factor (HIF)-$1{\alpha}$ or administering wheatgrass extract. Wheatgrass inhibited the hypoxia-mediated EMT by reducing the expression of phosphorylated Smad3 (pSmad3) and Snail. It suppressed the hypoxia-mediated EMT processes of airway epithelial cells via HIF-$1{\alpha}$ and the pSmad3 signaling pathway. CONCLUSION: These results suggest that wheatgrass has potential as a therapeutic or supplementary agent for HIF-1-related diseases.


Triticum;epithelial-mesenchymal transition;sinusitis;hypoxia inducible factor 1;cadherins


Supported by : Chosun University


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