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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

Abstract

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.

Keywords

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

Acknowledgement

Supported by : Chosun University

References

  1. Hsu YC, Kuo WR, Chen YY, Tai CF, Tsai CJ, Wang LF. Increased expression of hypoxia-inducible factor 1alpha in the nasal polyps. Am J Otolaryngol 2007;28:379-83. https://doi.org/10.1016/j.amjoto.2006.11.004
  2. Chien CY, Tai CF, Ho KY, Kuo WR, Chai CY, Hsu YC, Wang LF. Expression of hypoxia-inducible factor 1alpha in the nasal polyps by real-time RT-PCR and immunohistochemistry. Otolaryngol Head Neck Surg 2008;139:206-10. https://doi.org/10.1016/j.otohns.2008.04.022
  3. Thiery JP, Sleeman JP. Complex networks orchestrate epithelialmesenchymal transitions. Nat Rev Mol Cell Biol 2006;7:131-42. https://doi.org/10.1038/nrm1835
  4. Hackett TL, Warner SM, Stefanowicz D, Shaheen F, Pechkovsky DV, Murray LA, Argentieri R, Kicic A, Stick SM, Bai TR, Knight DA. Induction of epithelial-mesenchymal transition in primary airway epithelial cells from patients with asthma by transforming growth factor-beta1. Am J Respir Crit Care Med 2009;180:122-33. https://doi.org/10.1164/rccm.200811-1730OC
  5. Shin HW, Cho K, Kim DW, Han DH, Khalmuratova R, Kim SW, Jeon SY, Min YG, Lee CH, Rhee CS, Park JW. Hypoxia-inducible factor 1 mediates nasal polypogenesis by inducing epithelial-to-mesenchymal transition. Am J Respir Crit Care Med 2012;185:944-54. https://doi.org/10.1164/rccm.201109-1706OC
  6. Alitheen NB, Oon CL, Keong YS, Chuan TK, Li HK, Yong HW. Cytotoxic effects of commercial wheatgrass and fiber towards human acute promyelocytic leukemia cells (HL60). Pak J Pharm Sci 2011;24:243-50.
  7. Ferruzzi MG, Blakeslee J. Digestion, absorption, and cancer preventative activity of dietary chlorophyll derivatives. Nutr Res 2007;27:1-12. https://doi.org/10.1016/j.nutres.2006.12.003
  8. Das A, Raychaudhuri U, Chakraborty R. Effect of freeze drying and oven drying on antioxidant properties of fresh wheatgrass. Int J Food Sci Nutr 2012;63:718-21. https://doi.org/10.3109/09637486.2011.644769
  9. Kulkarni SD, Tilak JC, Acharya R, Rajurkar NS, Devasagayam TP, Reddy AV. Evaluation of the antioxidant activity of wheatgrass (Triticum aestivum L.) as a function of growth under different conditions. Phytother Res 2006;20:218-27. https://doi.org/10.1002/ptr.1838
  10. Ben-Arye E, Goldin E, Wengrower D, Stamper A, Kohn R, Berry E. Wheat grass juice in the treatment of active distal ulcerative colitis: a randomized double-blind placebo-controlled trial. Scand J Gastroenterol 2002;37:444-9. https://doi.org/10.1080/003655202317316088
  11. Shermer M. Wheatgrass juice and folk medicine. Sci Am 2008;299:42.
  12. Steinke JW, Woodard CR, Borish L. Role of hypoxia in inflammatory upper airway disease. Curr Opin Allergy Clin Immunol 2008;8:16-20. https://doi.org/10.1097/ACI.0b013e3282f3f488
  13. Matsune S, Kono M, Sun D, Ushikai M, Kurono Y. Hypoxia in paranasal sinuses of patients with chronic sinusitis with or without the complication of nasal allergy. Acta Otolaryngol 2003;123:519-23. https://doi.org/10.1080/0036554021000028113
  14. Lu X, Zhang XH, Wang H, Long XB, You XJ, Gao QX, Cui YH, Liu Z. Expression of osteopontin in chronic rhinosinusitis with and without nasal polyps. Allergy 2009;64:104-11. https://doi.org/10.1111/j.1398-9995.2008.01829.x
  15. Shakya G, Balasubramanian S, Rajagopalan R. Methanol extract of wheatgrass induces G1 cell cycle arrest in a p53-dependent manner and down regulates the expression of cyclin D1 in human laryngeal cancer cells-an in vitro and in silico approach. Pharmacogn Mag 2015;11:S139-47. https://doi.org/10.4103/0973-1296.157715
  16. Chiu LC, Kong CK, Ooi VE. The chlorophyllin-induced cell cycle arrest and apoptosis in human breast cancer MCF-7 cells is associated with ERK deactivation and Cyclin D1 depletion. Int J Mol Med 2005;16:735-40.
  17. Aydos SE, Avci A, Ozkan T, Karadag A, Gurleyik E, Altinok B, Sunguroglu A. Antiproliferative, apoptotic and antioxidant activities of wheatgrass (Triticum aestivum L.) extract on CML (K562) cell line. Turk J Med Sci 2011;41:657-63.
  18. Lam CR, Brush BE. Chlorophyll and wound healing; experimental and clinical study. Am J Surg 1950;80:204-10. https://doi.org/10.1016/0002-9610(50)90531-9
  19. Shakya G, Randhi PK, Pajaniradje S, Mohankumar K, Rajagopalan R. Hypoglycaemic role of wheatgrass and its effect on carbohydrate metabolic enzymes in type II diabetic rats. Toxicol Ind Health 2016;32:1026-32. https://doi.org/10.1177/0748233714545202
  20. Jaya MS, Gayathri S. Antioxidant activity of wheat grass and impact of supplementing grass extract on anaemics. Biomed 2009;4:262-8.

Cited by

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  2. Retraction: Wheatgrass extract inhibits hypoxia-inducible factor-1-mediated epithelial-mesenchymal transition in A549 cells vol.12, pp.3, 2018, https://doi.org/10.4162/nrp.2018.12.3.265