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D-葡萄糖胺通过抑制DU145前列腺癌细胞中的蛋白质翻译来下调缺氧诱导因子-1α（HIF-1α）。

D-glucosamine down-regulates HIF-1alpha through inhibition of protein translation in DU145 prostate cancer cells.

作者信息

Park Jee-Young, Park Jong-Wook, Suh Seong-Il, Baek Won-Ki

机构信息

Chronic Disease Research Center, School of Medicine, Keimyung University, 194 Dongsan-Dong, Jung-Gu, Daegu 700-712, Republic of Korea.

出版信息

Biochem Biophys Res Commun. 2009 Apr 24;382(1):96-101. doi: 10.1016/j.bbrc.2009.02.129. Epub 2009 Feb 28.

DOI:10.1016/j.bbrc.2009.02.129
PMID:19254699
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)-1alpha expression. D-glucosamine caused a decreased expression of HIF-1alpha under normoxic and hypoxic conditions without affecting HIF-1alpha mRNA expression in DU145 prostate cancer cells. D-glucosamine inhibited HIF-1alpha accumulation induced by proteasome inhibitor MG132 and prolyl hydroxylase inhibitor DMOG suggesting D-glucosamine reduces HIF-1alpha protein expression through proteasome-independent pathway. Metabolic labeling assays indicated that D-glucosamine inhibits translation of HIF-1alpha protein. In addition, D-glucosamine inhibited HIF-1alpha expression induced by serum stimulation in parallel with inhibition of p70S6K suggesting D-glucosamine inhibits growth factor-induced HIF-1alpha expression, at least in part, through p70S6K inhibition. Taken together, these results suggest that D-glucosamine inhibits HIF-1alpha expression through inhibiting protein translation and provide new insight into a potential mechanism of the anticancer properties of D-glucosamine.

摘要

据报道，D-葡萄糖胺在体外培养和体内均可抑制癌细胞的增殖。在本研究中，我们报告了一种对D-葡萄糖胺的新反应，涉及缺氧诱导因子（HIF）-1α表达的翻译调控。在常氧和缺氧条件下，D-葡萄糖胺均可导致DU145前列腺癌细胞中HIF-1α表达降低，而不影响HIF-1α mRNA的表达。D-葡萄糖胺可抑制蛋白酶体抑制剂MG132和脯氨酰羟化酶抑制剂DMOG诱导的HIF-1α积累，这表明D-葡萄糖胺通过非蛋白酶体途径降低HIF-1α蛋白表达。代谢标记分析表明，D-葡萄糖胺可抑制HIF-1α蛋白的翻译。此外，D-葡萄糖胺在抑制p70S6K的同时，也抑制了血清刺激诱导的HIF-1α表达，这表明D-葡萄糖胺至少部分通过抑制p70S6K来抑制生长因子诱导的HIF-1α表达。综上所述，这些结果表明D-葡萄糖胺通过抑制蛋白质翻译来抑制HIF-1α表达，并为D-葡萄糖胺抗癌特性的潜在机制提供了新的见解。