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Article

Short-term treatment with glucosamine hydrochloride specifically downregulates hypoxia-inducible factor-1α at the protein level in YD-8 human tongue cancer cells

  • Authors:
    • Jeong-Rang Jo
    • Yu-Kyoung Park
    • Byeong-Churl Jang
  • View Affiliations / Copyright

    Affiliations: Department of Molecular Medicine, College of Medicine, Keimyung University, Dalseo-gu 704-701, Republic of Korea
  • Pages: 1699-1706
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    Published online on: March 11, 2014
       https://doi.org/10.3892/ijo.2014.2336
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Abstract

Hypoxia-inducible factor-1 (HIF-1) is a tumor angiogenic transcription factor composed of an α and β subunit. We investigated the effect of glucosamine hydrochloride (GS-HCl) on the expression of HIF-1α and HIF-1β in serum‑treated YD-8 human tongue cancer cells. While long-term (24 h) treatment with GS-HCl strongly repressed the expression of HIF-1α and HIF-1β at both the protein and mRNA levels, short-term (4 h) GS-HCl treatment inhibited HIF-1α at the protein level. Short-term GS-HCl treatment also decreased phosphorylation of p70S6K and S6, translation-related proteins. However, the results of subsequent pharmacological inhibition and protein stability analyses indicated that HIF-1α protein downregulation induced by short-term GS-HCl treatment was not through modulation of the mTOR/p70S6K/S6 signaling pathways, the 26S proteasomal and lysosomal activities and HIF-1α protein stability. Importantly, our further analyses identified that HIF-1α protein downregulation induced by short-term GS-HCl treatment was blunted by exogenous administration of the citric acid cycle metabolites citrate and 2-oxoglutarate, but not the glycolytic end byproducts pyruvate and lactate. These findings demonstrate firstly that short-term GS treatment selectively downregulates HIF-1α at the protein level in YD-8 cells via interference of production of the citric acid cycle metabolites. It is proposed that short-term GS-HCl exposure may be applied for the treatment of oral tumors with high expression of HIF-1α.
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Copy and paste a formatted citation
Spandidos Publications style
Jo J, Park Y and Jang B: Short-term treatment with glucosamine hydrochloride specifically downregulates hypoxia-inducible factor-1α at the protein level in YD-8 human tongue cancer cells. Int J Oncol 44: 1699-1706, 2014.
APA
Jo, J., Park, Y., & Jang, B. (2014). Short-term treatment with glucosamine hydrochloride specifically downregulates hypoxia-inducible factor-1α at the protein level in YD-8 human tongue cancer cells. International Journal of Oncology, 44, 1699-1706. https://doi.org/10.3892/ijo.2014.2336
MLA
Jo, J., Park, Y., Jang, B."Short-term treatment with glucosamine hydrochloride specifically downregulates hypoxia-inducible factor-1α at the protein level in YD-8 human tongue cancer cells". International Journal of Oncology 44.5 (2014): 1699-1706.
Chicago
Jo, J., Park, Y., Jang, B."Short-term treatment with glucosamine hydrochloride specifically downregulates hypoxia-inducible factor-1α at the protein level in YD-8 human tongue cancer cells". International Journal of Oncology 44, no. 5 (2014): 1699-1706. https://doi.org/10.3892/ijo.2014.2336
Copy and paste a formatted citation
x
Spandidos Publications style
Jo J, Park Y and Jang B: Short-term treatment with glucosamine hydrochloride specifically downregulates hypoxia-inducible factor-1α at the protein level in YD-8 human tongue cancer cells. Int J Oncol 44: 1699-1706, 2014.
APA
Jo, J., Park, Y., & Jang, B. (2014). Short-term treatment with glucosamine hydrochloride specifically downregulates hypoxia-inducible factor-1α at the protein level in YD-8 human tongue cancer cells. International Journal of Oncology, 44, 1699-1706. https://doi.org/10.3892/ijo.2014.2336
MLA
Jo, J., Park, Y., Jang, B."Short-term treatment with glucosamine hydrochloride specifically downregulates hypoxia-inducible factor-1α at the protein level in YD-8 human tongue cancer cells". International Journal of Oncology 44.5 (2014): 1699-1706.
Chicago
Jo, J., Park, Y., Jang, B."Short-term treatment with glucosamine hydrochloride specifically downregulates hypoxia-inducible factor-1α at the protein level in YD-8 human tongue cancer cells". International Journal of Oncology 44, no. 5 (2014): 1699-1706. https://doi.org/10.3892/ijo.2014.2336
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