title: Curcumin inhibits neurotensin-mediated interleukin-8 production and migration of HCT116 human colon cancer cells.
abstract: OBJECTIVE
  Neurotensin, a gut tridecapeptide, acts as a potent cellular mitogen for various colorectal and pancreatic cancers that possess high-affinity neurotensin receptors. Cytokine/chemokine proteins are increasingly recognized as important local factors that play a role in the metastasis and invasion of multiple cancers. The purpose of this study was to (a) determine the effect of neurotensin on cytokine/chemokine gene expression and cell migration in human cancer cells and (b) assess the effect of curcumin, a natural dietary product, on neurotensin-mediated processes.
  
  
  METHODS
  The human colorectal cancer, HCT116, was treated with neurotensin, with or without curcumin, and interleukin (IL)-8 expression and protein secretion was measured. Signaling pathways, which contribute to the effects of neurotensin, were assessed. Finally, the effect of curcumin on neurotensin-mediated HCT116 cell migration was analyzed.
  
  
  RESULTS
  We show that neurotensin, acting through the native high-affinity neurotensin receptor, induced IL-8 expression in human colorectal cancer cells in a time- and dose-dependent fashion. This stimulation involves Ca2+-dependent protein kinase C, extracellular signal-regulated kinase-dependent activator protein-1, and extracellular signal-regulated kinase-independent nuclear factor-kappaB pathways. Curcumin inhibited neurotensin-mediated activator protein-1 and nuclear factor-kappaB activation and Ca2+ mobilization. Moreover, curcumin blocked neurotensin-stimulated IL-8 gene induction and protein secretion and, at a low concentration (i.e., 10 micromol/L), blocked neurotensin-stimulated colon cancer cell migration.
  
  
  CONCLUSIONS
  Neurotensin-mediated induction of tumor cell IL-8 expression and secretion may contribute to the procarcinogenic effects of neurotensin on gastrointestinal cancers. Furthermore, a potential mechanism for the chemopreventive and chemotherapeutic effects of curcumin on colon cancers may be through the inhibition of gastrointestinal hormone (e.g., neurotensin)-induced chemokine expression and cell migration.
authors.affiliation: Department of Surgery and The Sealy Center for Cancer Cell Biology, The University of Texas Medical Branch, Galveston, Texas 77555-0536, USA.
authors.forename: Xiaofu
authors.initials: X
authors.lastname: Wang
authors.forename: Qingding
authors.initials: Q
authors.lastname: Wang
authors.forename: Kirk L
authors.initials: KL
authors.lastname: Ives
authors.forename: B Mark
authors.initials: BM
authors.lastname: Evers
mesh_terms: D002118:Calcium / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects*; D003110:Colonic Neoplasms / Q000378:metabolism; D003474:Curcumin / Q000494:pharmacology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects; D045325:HCT116 Cells; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000378:metabolism; D016328:NF-kappa B / Q000502:physiology; D009496:Neurotensin / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000502:physiology; D015533:Transcriptional Activation
chemical_list: D016209:Interleukin-8; D016328:NF-kappa B; D018808:Transcription Factor AP-1; D009496:Neurotensin; D011493:Protein Kinase C; D048049:Extracellular Signal-Regulated MAP Kinases; D003474:Curcumin; D002118:Calcium