Glucosamine Inhibits IL-1β-Mediated IL-8 Production in Prostate Cancer Cells by MAPK Attenuation

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-1 beta 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-1 beta regulates IL-8 expression in prostate cancer cells. Glucosamine is widely regarded as an anti-inflammatory agent and thus we hypothesized that if IL-1 beta 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-1 beta and glucosamine on IL-8 expression using ELISA and RT-PCR analyses. IL-1 beta elevated IL-8 mRNA expression and subsequent IL-8 secretion. Glucosamine significantly inhibited IL-1 beta-induced IL-8 secretion. IL-8 appeared to induce LNCaP cell proliferation by MTT assay; involvement of IL-8 in IL-1 beta-dependent PC-3 cell migration was demonstrated by wound-healing and transwell migration assays. Inhibitors of MAPKs and NF kappa B were used to pinpoint MAPKs but not NF kappa B being involved in IL-10-mediated IL-8 production. IL-10-provoked phosphorylation of all MAPKs was notably suppressed by glucosamine. We suggest that IL-1 beta 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-1 beta-mediated activation of MAPKs and therefore reduces IL-8 production; this, in turn, attenuates cell proliferation/migration. J. Cell. Biochem. 108: 489-498, 2009. (C) 2009 Wiley-Liss, Inc.