title: N-3 polyunsaturated fatty acids inhibit IFN-γ-induced IL-18 binding protein production by prostate cancer cells.
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.
authors.affiliation: Department of Agricultural, Food and Nutritional Science, University of Alberta, 116 Street and 85 Avenue, Edmonton, AB, T6G 2R3, Canada, wxfzuowei@gmail.com.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Wang
authors.forename: Andrew
authors.initials: A
authors.lastname: Breeze
authors.forename: Marianna
authors.initials: M
authors.lastname: Kulka
mesh_terms: D045744:Cell Line, Tumor; D015525:Fatty Acids, Omega-3 / Q000378:metabolism* / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis* / Q000235:genetics; D007371:Interferon-gamma / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D017471:Receptors, Interferon / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D000096743:Interferon gamma Receptor
chemical_list: D015525:Fatty Acids, Omega-3; D036341:Intercellular Signaling Peptides and Proteins; D007371:Interferon-gamma; D012333:RNA, Messenger; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor; C118370:interleukin-18 binding protein