Glucosamine inhibits IL-1beta-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-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.
Tsai
Cheng-Yen
CY
Department of Physiology, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
Lee
Tzong-Shyuan
TS
Kou
Yu Ru
YR
Wu
Yuh-Lin
YL
D000704:Analysis of Variance; D000893:Anti-Inflammatory Agents / Q000378:metabolism / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002470:Cell Survival; D018920:Coculture Techniques; D015972:Gene Expression Regulation, Neoplastic; D005944:Glucosamine / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism* / Q000494:pharmacology; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D010766:Phosphorylation; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D023062:Receptors, Interleukin-8A / Q000235:genetics / Q000378:metabolism; D023063:Receptors, Interleukin-8B / Q000235:genetics / Q000378:metabolism; D013997:Time Factors
D000893:Anti-Inflammatory Agents; D053583:Interleukin-1beta; D016209:Interleukin-8; D016328:NF-kappa B; D012333:RNA, Messenger; D023062:Receptors, Interleukin-8A; D023063:Receptors, Interleukin-8B; D020928:Mitogen-Activated Protein Kinases; D005944:Glucosamine