Cancer Immunology, Immunotherapy

, Volume 64, Issue 2, pp 249–258 | Cite as

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

  • Xiaofeng Wang
  • Andrew Breeze
  • Marianna KulkaEmail author
Original Article


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.


N-3 PUFAs IFN-γ signaling IL-18 binding protein Prostate cancer cells 



Interferon-γ receptor




IL-18 binding protein


Docosahexaenoic acid


Docosapentaenoic acid


Enzyme-linked immunosorbent assay


Eicosapentaenoic acid


Extracellular signal-regulated kinase


Glyceraldehyde 3-phosphate dehydrogenase


Gas chromatography–mass spectrometry


Janus kinase


c-Jun N-terminal kinase


Major histocompatibility complex


Natural killer


Phosphate-buffered saline


Peroxisome proliferator-activated receptors


Polyunsaturated fatty acids


Quantitative polymerase chain reaction


Src homology


Signal transducers and activators of transcription


Tris-buffered saline


TBS containing 0.05 % tween-20


T helper


Tumor necrosis factor



We thank Dr. Adriana Catalli for technical support. This work was supported by The Canadian Institute for Health Research, the National Research Council Canada, and the Canadian Breast Cancer Foundation-Atlantic.

Conflict of interest

The authors declare that they have no conflicts of interest.

Supplementary material

262_2014_1630_MOESM1_ESM.pdf (307 kb)
Supplementary material 1 (PDF 306 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Xiaofeng Wang
    • 1
  • Andrew Breeze
    • 2
  • Marianna Kulka
    • 2
    • 3
    • 4
    Email author
  1. 1.Department of Agricultural, Food and Nutritional ScienceUniversity of AlbertaEdmontonCanada
  2. 2.National Research Council CanadaEdmontonCanada
  3. 3.Department of Medical Microbiology and ImmunologyUniversity of AlbertaEdmontonCanada
  4. 4.National Institute for NanotechnologyEdmontonCanada

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