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

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Author(s)
JEONG-RANG JOYU-KYOUNG PARKBYEONG-CHURL JANG
Keimyung Author(s)
Jang, Byeong Churl
Department
Dept. of Molecular Medicine (분자의학)
Journal Title
International Journal of Oncology
Issued Date
2014
Volume
44
Issue
5
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.
Keimyung Author(s)(Kor)
장병철
Publisher
School of Medicine
Citation
JEONG-RANG JO et al. (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(5), 1699–1706. doi: 10.3892/ijo.2014.2336
Type
Article
ISSN
1019-6439
Source
http://www.spandidos-publications.com/ijo/44/5/1699
DOI
10.3892/ijo.2014.2336
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/36006
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Molecular Medicine (분자의학)
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