Transforming growth factor-β1 induces glutathione peroxidase-1 and protects from H2O2-induced cell death in colon cancer cells via the Smad2/ERK1/2/HIF-1α pathway

  • Authors:
    • Ying Huang
    • Wenfeng Fang
    • Yulei Wang
    • Wancai Yang
    • Bin Xiong
  • View Affiliations

  • Published online on: February 3, 2012     https://doi.org/10.3892/ijmm.2012.901
  • Pages: 906-912
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Abstract

Recent studies have shown that transforming growth factor-β1 (TGF-β1) signaling plays important roles in the redox system in benign and malignant cells. Whether TGF-β mediates an antioxidative damage response in colorectal cancer cells is largely unknown. Herein, using the human colorectal cancer cell lines we found that TGF-β1 induced glutathione peroxidase-1 (GPx-1) expression and enzyme activity, and that the upregulation of GPx-1 by TGF-β1 could protect colorectal cell lines from H2O2-induced oxidation damage. Further, we used loss- and gain-function approaches to elucidate the underlying mechanism and found that TGF-β1 induced GPx-1 through activation of the TGF-β receptor type I (TGF-βRI)/Smad2/extracellular-signal-regulated kinase 1/2 (ERK1/2)/hypoxia-inducible factor-1α (HIF-1α) signaling pathway. This cascade could be blocked by the TGF-βRI inhibitor or ERK1/2 inhibitor. Taken together, our data demonstrated that TGF-β1 induced GPx-1 expression and enzymatic activity via the TGF-βRI/Smad2/ERK1/2/HIF-1α signaling pathway, suggesting a novel antioxidative protective function of TGF-β1 in colorectal cancer cells.

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May 2012
Volume 29 Issue 5

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Huang Y, Fang W, Wang Y, Yang W and Xiong B: Transforming growth factor-β1 induces glutathione peroxidase-1 and protects from H2O2-induced cell death in colon cancer cells via the Smad2/ERK1/2/HIF-1α pathway. Int J Mol Med 29: 906-912, 2012
APA
Huang, Y., Fang, W., Wang, Y., Yang, W., & Xiong, B. (2012). Transforming growth factor-β1 induces glutathione peroxidase-1 and protects from H2O2-induced cell death in colon cancer cells via the Smad2/ERK1/2/HIF-1α pathway. International Journal of Molecular Medicine, 29, 906-912. https://doi.org/10.3892/ijmm.2012.901
MLA
Huang, Y., Fang, W., Wang, Y., Yang, W., Xiong, B."Transforming growth factor-β1 induces glutathione peroxidase-1 and protects from H2O2-induced cell death in colon cancer cells via the Smad2/ERK1/2/HIF-1α pathway". International Journal of Molecular Medicine 29.5 (2012): 906-912.
Chicago
Huang, Y., Fang, W., Wang, Y., Yang, W., Xiong, B."Transforming growth factor-β1 induces glutathione peroxidase-1 and protects from H2O2-induced cell death in colon cancer cells via the Smad2/ERK1/2/HIF-1α pathway". International Journal of Molecular Medicine 29, no. 5 (2012): 906-912. https://doi.org/10.3892/ijmm.2012.901