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)-1 alpha expression. D-Glucosamine Caused a decreased expression of HIF-1 alpha under normoxic and hypoxic conditions without affecting HIF-1 alpha mRNA expression in DU145 prostate cancer cells. D-Glucosamine inhibited HIF-1 alpha accumulation induced by proteasome inhibitor MG132 and prolyl hydroxylase inhibitor DMOG Suggesting D-glucosamine reduces HIF-1 alpha protein expression through proteasome-independent pathway. Metabolic labeling assays indicated that D-glucosamine inhibits translation of HIF-1 alpha protein. In addition, D-glucosamine inhibited HIF-1 alpha expression induced by serum stimulation in parallel with inhibition of p70S6K suggesting D-glucosamine inhibits growth factor-induced HIF-1 alpha expression,at least in part, through p70S6K inhibition. Taken together, these results suggest that D-glucosamine inhibits HIF-1 alpha. expression through inhibiting protein translation and provide new insight into a potential mechanism of the anticancer properties Of D-glucosamine. (C) 2009 Elsevier Inc. All rights reserved.