title: Anti-cancer activity of glucosamine through inhibition of N-linked glycosylation.
abstract: BACKGROUND
  We have reported that the glucosamine suppressed the proliferation of the human prostate carcinoma cell line DU145 through inhibition of STAT3 signaling. DU145 cells autonomously express IL-6 and the IL-6/STAT3 signaling is activated. IL-6 receptor subunits are subject to N-glycosylation, a posttranslational modification which is important for protein stability and function. We speculated that the inhibition of STAT3 phosphorylation by glucosamine might be a functional consequence of the reduced N-glycosylation of gp130.
  
  
  METHODS
  The human prostate cancer cell lines DU145 and PC-3 and human melanoma cell line A2058 were used in this study. Glucosamine effects on N-glycosylation of glycoproteins were determined by Western blot analysis. IL-6 binding to DU145 cells was analyzed by flow cytometry. The cell proliferation suppression was investigated by colorimetric Janus green staining method.
  
  
  RESULTS
  In DU145 cells glucosamine reduced the N-glycosylation of gp130, decreased IL-6 binding to cells and impaired the phosphorylation of JAK2, SHP2 and STAT3. Glucosamine acts in a very similar manner to tunicamycin, an inhibitor of protein N-glycosylation. Glucosamine-mediated inhibition of N-glycosylation was neither protein- nor cell-specific. Sensitivity of DU145, A2058 and PC-3 cells to glucosamine-induced inhibition of N-glycosylation were well correlated to glucosamine cytotoxicity in these cells.
  
  
  CONCLUSIONS
  Our results suggested that the glucosamine-induced global inhibition of protein N-glycosylation might be the basic mechanism underlying its multiple biochemical and cellular effects.
authors.affiliation: Department of Molecular and Cellular Biology, Beckman Research Institute of City of Hope National Medical Center, 1500 East Duarte Road, Duarte, California 91010, USA.
authors.forename: Viktor
authors.initials: V
authors.lastname: Chesnokov
authors.affiliation: Department of Molecular and Cellular Biology, Beckman Research Institute of City of Hope National Medical Center, 1500 East Duarte Road, Duarte, California 91010, USA.
authors.forename: Beata
authors.initials: B
authors.lastname: Gong
authors.affiliation: Department of Molecular and Cellular Biology, Beckman Research Institute of City of Hope National Medical Center, 1500 East Duarte Road, Duarte, California 91010, USA.
authors.forename: Chao
authors.initials: C
authors.lastname: Sun
authors.affiliation: Department of Molecular and Cellular Biology, Beckman Research Institute of City of Hope National Medical Center, 1500 East Duarte Road, Duarte, California 91010, USA.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Itakura
keywords: Cancer; Glucosamine; IL-6; N-linked glycosylation; STAT3