Anti‑lung cancer effect of glucosamine by suppressing the phosphorylation of FOXO

  • Authors:
    • Zhanwu Yu
    • Yinghua Ju
    • Hongxu Liu
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  • Published online on: July 14, 2017     https://doi.org/10.3892/mmr.2017.6976
  • Pages: 3395-3400
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Abstract

Lung cancer is the most common cause of cancer‑associated mortality worldwide, and glucosamine has the potential to exhibit antitumor activity. To reveal its anti‑lung cancer mechanism, the present study investigated the effect of glucosamine on the transcriptional activity of forkhead box O (FOXO)1 and FOXO3, and associated signal transduction pathways in A549 cells. An MTT assay was performed to investigate cell viability and immunoblotting was performed to detect protein levels of FOXO1/3, phosphorylated (p)‑FOXO1/3, AKT, p‑AKT, extracellular signal‑regulated kinase (ERK) and p‑ERK, and the levels of β‑O‑linked N‑acetylglucosamine (O‑GlcNAc)‑modified FOXO1 protein. Immunoprecipitation was performed to purify O‑GlcNAc‑modified protein prior to immunoblotting. Glucosamine inhibited FOXO1‑ and FOXO3‑specific amino acid phosphorylation, which was correlated with its translocation from the nucleus to cytoplasm, indicating a possible anti‑lung cancer mechanism of glucosamine. The present study also examined the phosphoinositide 3‑kinase (PI3K)/AKT and mitogen‑activated protein kinase (MAPK)/ERK pathways, which induce FOXO1‑ and FOXO3‑specific site phosphorylation. The data showed that glucosamine suppressed the translocation of FOXO from the cytoplasm to the nucleus via glucosamine‑induced O‑GlcNAc modification. These observations suggested that glucosamine modulated A549 cell proliferation, possibly via O‑GlcNAc modification‑induced downregulation of the PI3K/AKT and MAPK/ERK pathways and their downstream signaling molecules, FOXO1 and FOXO3.
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September-2017
Volume 16 Issue 3

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Yu Z, Ju Y and Liu H: Anti‑lung cancer effect of glucosamine by suppressing the phosphorylation of FOXO. Mol Med Rep 16: 3395-3400, 2017.
APA
Yu, Z., Ju, Y., & Liu, H. (2017). Anti‑lung cancer effect of glucosamine by suppressing the phosphorylation of FOXO. Molecular Medicine Reports, 16, 3395-3400. https://doi.org/10.3892/mmr.2017.6976
MLA
Yu, Z., Ju, Y., Liu, H."Anti‑lung cancer effect of glucosamine by suppressing the phosphorylation of FOXO". Molecular Medicine Reports 16.3 (2017): 3395-3400.
Chicago
Yu, Z., Ju, Y., Liu, H."Anti‑lung cancer effect of glucosamine by suppressing the phosphorylation of FOXO". Molecular Medicine Reports 16, no. 3 (2017): 3395-3400. https://doi.org/10.3892/mmr.2017.6976