N-3 polyunsaturated fatty acids inhibit IFN-γ-induced IL-18 binding protein production by prostate cancer cells

From National Research Council Canada

DOIResolve DOI: https://doi.org/10.1007/s00262-014-1630-z
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Name affiliation
  1. National Research Council Canada. Aquatic and Crop Resource Development
  2. NINT
FormatText
TypeArticle
Journal titleCancer Immunology, Immunotherapy
ISSN0340-7004
Volume64
Issue2
Pages249–258; # of pages: 10
Subjectgamma interferon; gamma interferon receptor; interleukin 18 binding protein; Janus kinase 1; messenger RNA; mitogen activated protein kinase 1; omega 3 fatty acid; STAT1 protein; synaptophysin; gamma interferon; gamma interferon receptor; interferon receptor; interleukin-18 binding protein; messenger RNA; signal peptide; cancer cell; cytokine production; immune response; prostate cancer; protein binding; protein expression; protein phosphorylation; signal transduction; biosynthesis; drug effects; gene expression regulation; genetics; metabolism; prostate tumor; tumor cell line; Gene Expression Regulation, Neoplastic; Intercellular Signaling Peptides and Proteins; Prostatic Neoplasms
Abstract
Prostate cancer cells can produce IL-18 binding protein (IL-18BP) in response to interferon-γ (IFN-γ), which may function to neutralize IL-18, an anti-tumor factor formerly known as IFN-γ inducing factor. The consumption of n-3 polyunsaturated fatty acids (PUFAs) has been associated with a lower risk of certain types of cancer including prostate cancer, although the precise mechanisms of this effect are poorly understood. We hypothesized that n-3 PUFAs could modify IL-18BP production by prostate cancer cells by altering IFN-γ receptor-mediated signal transduction. Here, we demonstrate that n-3 PUFA treatment significantly reduced IFN-γ-induced IL-18BP production by DU-145 and PC-3 prostate cancer cells by inhibiting IL-18BP mRNA expression and was associated with a reduction in IFN-γ receptor expression. Furthermore, IFN-γ-induced phosphorylation of Janus kinase 1 (JAK1), signal transducers and activators of transcription 1 (STAT1), extracellular signal-regulated kinases 1/2 (ERK1/2), and P38 were suppressed by n-3 PUFA treatment. By contrast, n-6 PUFA had no effect on IFN-γ receptor expression, but decreased IFN-γ-induced IL-18BP production and IFN-γ stimulation of JAK1, STAT1, ERK1/2, and JNK phosphorylation. These data indicate that both n-3 and n-6 PUFAs may be beneficial in prostate cancer by altering IFN-γ signaling, thus inhibiting IL-18BP production and thereby rendering prostate cancer cells more sensitive to IL-18-mediated immune responses.
Publication date
PublisherSpringer International Publishing
Terms of use
LanguageEnglish
Peer reviewedYes
NPARC number21275462
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Record created2015-07-14
Record modified2016-05-09
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