Glucosamine inhibits IL-1beta-mediated IL-8 production in prostate cancer cells by MAPK attenuation

J Cell Biochem. 2009 Oct 1;108(2):489-98. doi: 10.1002/jcb.22278.


Inflammation is a complex process involving cytokine production to regulate host defense cascades. In contrast to the therapeutic significance of acute inflammation, a pathogenic impact of chronic inflammation on cancer development has been proposed. Upregulation of inflammatory cytokines, such as IL-1beta and IL-8, has been noted in prostate cancer patients and IL-8 has been shown to promote prostate cancer cell proliferation and migration; however, it is not clear whether IL-1beta regulates IL-8 expression in prostate cancer cells. Glucosamine is widely regarded as an anti-inflammatory agent and thus we hypothesized that if IL-1beta activated IL-8 production in prostate cancer cells, then glucosamine ought to blunt such an effect. Three prostate cancer cell lines, DU-145, PC-3, and LNCaP, were used to evaluate the effects of IL-1beta and glucosamine on IL-8 expression using ELISA and RT-PCR analyses. IL-1beta elevated IL-8 mRNA expression and subsequent IL-8 secretion. Glucosamine significantly inhibited IL-1beta-induced IL-8 secretion. IL-8 appeared to induce LNCaP cell proliferation by MTT assay; involvement of IL-8 in IL-1beta-dependent PC-3 cell migration was demonstrated by wound-healing and transwell migration assays. Inhibitors of MAPKs and NFkappaB were used to pinpoint MAPKs but not NFkappaB being involved in IL-1beta-mediated IL-8 production. IL-1beta-provoked phosphorylation of all MAPKs was notably suppressed by glucosamine. We suggest that IL-1beta can activate the MAPK pathways resulting in an induction of IL-8 production, which promotes prostate cancer cell proliferation and migration. In this context, glucosamine appears to inhibit IL-1beta-mediated activation of MAPKs and therefore reduces IL-8 production; this, in turn, attenuates cell proliferation/migration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Anti-Inflammatory Agents / metabolism
  • Anti-Inflammatory Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Cell Survival
  • Coculture Techniques
  • Gene Expression Regulation, Neoplastic
  • Glucosamine / metabolism
  • Glucosamine / pharmacology*
  • Humans
  • Interleukin-1beta / metabolism*
  • Interleukin-1beta / pharmacology
  • Interleukin-8 / genetics
  • Interleukin-8 / metabolism*
  • Male
  • Mitogen-Activated Protein Kinases / antagonists & inhibitors*
  • Mitogen-Activated Protein Kinases / metabolism
  • NF-kappa B / antagonists & inhibitors
  • Phosphorylation
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / metabolism*
  • RNA, Messenger / metabolism
  • Receptors, Interleukin-8A / genetics
  • Receptors, Interleukin-8A / metabolism
  • Receptors, Interleukin-8B / genetics
  • Receptors, Interleukin-8B / metabolism
  • Time Factors


  • Anti-Inflammatory Agents
  • Interleukin-1beta
  • Interleukin-8
  • NF-kappa B
  • RNA, Messenger
  • Receptors, Interleukin-8A
  • Receptors, Interleukin-8B
  • Mitogen-Activated Protein Kinases
  • Glucosamine