Curcumin inhibits neurotensin-mediated interleukin-8 production and migration of HCT116 human colon cancer cells

Xiaofu Wang, Qingding Wang, Kirk L. Ives, B. Mark Evers

Research output: Contribution to journalArticlepeer-review

102 Scopus citations

Abstract

Purpose: 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. Experimental Design: 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-κB pathways. Curcumin inhibited neurotensin-mediated activator protein-1 and nuclear factor-κB activation and Ca2+ mobilization. Moreover, curcumin blocked neurotensin-stimulated IL-8 gene induction and protein secretion and, at a low concentration (i.e., 10 μmol/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.

Original languageEnglish
Pages (from-to)5346-5355
Number of pages10
JournalClinical Cancer Research
Volume12
Issue number18
DOIs
StatePublished - Sep 15 2006

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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