Glucosamine induces cell death via proteasome inhibition in human ALVA41 prostate cancer cell

Glucosamine, a naturally occurring amino monosaccharide, has been reported to play a role in the regulation of apoptosis more than half century. However the effect of glucosamine on tumor cells and the involved molecular mechanisms have not been thoroughly investigated. Glucosamine enters the hexosamine biosynthetic pathway (HBP) downstream of the rate-limiting step catalyzed by the GFAT (glutamine:fluctose- 6-phosphate amidotransferase), providing UDPGlcNAc substrates for O-linked β-N-acetylglucosamine (O-GlcNAc) protein modification. Considering that O-GlcNAc modification of proteasome subunits inhibits its activity, we examined whether glucosamine induces growth inhibition via affecting proteasomal activity. In the present study, we found glucosamine inhibited proteasomal activity and the proliferation of ALVA41 prostate cancer cells. The inhibition of proteasomal activity results in the accumulation of ubiquitinated proteins, followed by induction of apoptosis. In addition, we demonstrated that glucosamine downregulated proteasome activator PA28γ and overexpression of PA28γ rescued the proteasomal activity and growth inhibition mediated by glucosamine. We further demonstrated that inhibition of O-GlcNAc abrogated PA28γ suppression induced by glucosamine. These findings suggest that glucosamine may inhibit growth of ALVA41 cancer cells through downregulation of PA28γ and inhibition of proteasomal activity via O-GlcNAc modification.     

一种新型葡萄糖基化竹红菌素的合成和ESR研究

以巯基乙酸取代的竹红菌乙素和氨基葡萄糖为反应物,只用一步就合成了一种新型葡萄糖修饰的竹红菌乙素.氨基葡萄糖的取代改善了竹红菌乙素的水溶性及其在光疗窗口的吸收,并保持了其产生¹O₂、O₂^·-、^·OH和半醌负离子自由基的光化学活性.