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

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