D-glucosamine down-regulates HIF-1alpha through inhibition of protein translation in DU145 prostate cancer cells.
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.
Park
Jee-Young
JY
Chronic Disease Research Center, School of Medicine, Keimyung University, 194 Dongsan-Dong, Jung-Gu, Daegu 700-712, Republic of Korea.
Park
Jong-Wook
JW
Suh
Seong-Il
SI
Baek
Won-Ki
WK
D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D015536:Down-Regulation; D005944:Glucosamine / Q000494:pharmacology*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D008297:Male; D011471:Prostatic Neoplasms / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects
D000970:Antineoplastic Agents; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D005944:Glucosamine