Saturated fatty acids up-regulate COX-2 expression in prostate epithelial cells via toll-like receptor 4/NF-κB signaling.
Cyclooxygenase-2 (COX-2) has been implicated in prostate carcinogenesis, and recently it has been confirmed to be a molecular target of saturated fatty acids (SFAs). In the present study, we investigated the effect of stearic acid (SA) and palmitic acid (PA), two of the most abundant SFAs contained in dietary fat, on COX-2 expression in prostate epithelial cells and the signaling transduction pathway involved. First, we demonstrated that both SA and PA increased the mRNA and protein expression of COX-2, and consistently induced the activation of NF-κB in RWPE-1, BPH-1 and PC-3 prostate epithelial cell lines. The effect of SA and PA on COX-2 over-expression and NF-κB activation was in a dose-dependent manner, and PA was more potent than SA at the same concentration. Then, we demonstrated inhibition of NF-κB using its specific inhibitor strikingly attenuated PA-induced COX-2 expression. Toll-like receptor 4 (TLR4) was revealed to be expressed on RWPE-1, BPH-1 and PC-3 cell lines by PCR and immunofluorescence staining, and blocking its signaling significantly inhibited PA induced COX-2 over-expression and NF-κB activation. Taken together, we demonstrated that SFAs can up-regulate COX-2 expression in prostate epithelial cells, and this effect was mediated mainly through the TLR4/NF-κB signaling pathway.
Department of Urology, Peking University First Hospital and Institute of Urology, Peking University, 100034, Beijing, China.
Jie
J
Liu
Shuai
S
Hu
Yun
Y
Cui
Meng-Kui
MK
Sun
Feng
F
Xie
Qian
Q
Zhang
Jie
J
Jin
D000818:Animals; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D019308:Palmitic Acid / Q000494:pharmacology*; D011467:Prostate / Q000187:drug effects* / Q000201:enzymology; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013229:Stearic Acids / Q000494:pharmacology*; D051197:Toll-Like Receptor 4 / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
D016328:NF-kappa B; D012333:RNA, Messenger; D013229:Stearic Acids; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D019308:Palmitic Acid; C031183:stearic acid; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human