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D-Glucosamine down-regulates HIF-1α through inhibition of protein translation in DU145 prostate cancer cells

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Author(s)
박종욱서성일백원기
Alternative Author(s)
Park, Jong WookSuh, Seong IlBaek, Won Ki
Publication Year
2009
Abstract
d-Glucosamine has been reported to inhibit proliferation of cancer cells in culture and in vivo. In this study we report a novel response to d-glucosamine involving the translation regulation of hypoxia inducible factor (HIF)-1α expression. d-Glucosamine caused a decreased expression of HIF-1α under normoxic and hypoxic conditions without affecting HIF-1α mRNA expression in DU145 prostate cancer cells. d-Glucosamine inhibited HIF-1α accumulation induced by proteasome inhibitor MG132 and prolyl hydroxylase inhibitor DMOG suggesting d-glucosamine reduces HIF-1α protein expression through proteasome-independent pathway. Metabolic labeling assays indicated that d-glucosamine inhibits translation of HIF-1α protein. In addition, d-glucosamine inhibited HIF-1α expression induced by serum stimulation in parallel with inhibition of p70S6K suggesting d-glucosamine inhibits growth factor-induced HIF-1α expression, at least in part, through p70S6K inhibition. Taken together, these results suggest that d-glucosamine inhibits HIF-1α expression through inhibiting protein translation and provide new insight into a potential mechanism of the anticancer properties of d-glucosamine.

Keywords
d-Glucosamine;
Hif-1α;
VEGF;
p70S6K;
Prostate cancer
Department
Dept. of Immunology (면역학)
Dept. of Microbiology (미생물학)
Publisher
School of Medicine
Citation
Biochemical and Biophysical Research Communications, Vol.382(1) : 96-101, 2009
Type
Article
ISSN
0006-291X
DOI
10.1016/j.bbrc.2009.02.129
URI
http://kumel.medlib.dsmc.or.kr/handle/2015.oak/35158
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