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Updated: May 31, 2026
Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
Published on: December 27, 2016
Glucosamine induces cell death via proteasome inhibition in human ALVA41 prostate cancer cell
Bao-Qin Liu1, Xin Meng, Chao Li
1Department of Biochemistry and Molecular Biology, Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang 110001, China.
Abstract:
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.
Insights
Glucosamine inhibits prostate cancer cell growth by reducing proteasomal activity and downregulating the PA28γ activator. This occurs through O-linked β-N-acetylglucosamine (O-GlcNAc) modification, leading to apoptosis.
Area of Science:
- Biochemistry
- Molecular Biology
- Cancer Research
Background:
- Glucosamine is a naturally occurring amino monosaccharide involved in apoptosis regulation.
- The effects of glucosamine on tumor cells and its molecular mechanisms remain incompletely understood.
- Glucosamine influences the hexosamine biosynthetic pathway (HBP) and O-linked β-N-acetylglucosamine (O-GlcNAc) protein modification.
Purpose of the Study:
- To investigate the effect of glucosamine on prostate cancer cell proliferation and proteasomal activity.
- To elucidate the molecular mechanisms underlying glucosamine-induced growth inhibition.
- To determine the role of O-GlcNAc modification and proteasome activator PA28γ in glucosamine's effects.
Main Methods:
- Treatment of ALVA41 prostate cancer cells with glucosamine.
- Assay of proteasomal activity and cell proliferation.
- Analysis of ubiquitinated protein accumulation and apoptosis induction.
- Measurement of PA28γ expression levels.
- Investigation of O-GlcNAc modification inhibition.
Main Results:
- Glucosamine inhibited proteasomal activity and proliferation in ALVA41 prostate cancer cells.
- Glucosamine treatment led to the accumulation of ubiquitinated proteins and induced apoptosis.
- Glucosamine downregulated proteasome activator PA28γ.
- Overexpression of PA28γ rescued the effects of glucosamine on proteasomal activity and cell growth.
- Inhibition of O-GlcNAc modification abrogated glucosamine-induced PA28γ suppression.
Conclusions:
- Glucosamine inhibits ALVA41 prostate cancer cell growth by suppressing proteasomal activity.
- The mechanism involves the downregulation of PA28γ, potentially mediated by O-GlcNAc modification.
- Glucosamine-induced apoptosis is linked to proteasomal inhibition and protein ubiquitination.
