Anti-inflammatory effects of nobiletin on TLR4/TRIF/IRF3 and TLR9/IRF7 signaling pathways in prostate cancer cells


Deveci Ozkan A., Kaleli S., Onen H. I., SARIHAN M., Guney Eskiler G., Kalayci Yigin A., ...Daha Fazla

IMMUNOPHARMACOLOGY AND IMMUNOTOXICOLOGY, cilt.42, sa.2, ss.93-100, 2020 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 42 Sayı: 2
  • Basım Tarihi: 2020
  • Doi Numarası: 10.1080/08923973.2020.1725040
  • Dergi Adı: IMMUNOPHARMACOLOGY AND IMMUNOTOXICOLOGY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Aquatic Science & Fisheries Abstracts (ASFA), BIOSIS, CAB Abstracts, EMBASE, Food Science & Technology Abstracts, MEDLINE, Veterinary Science Database
  • Sayfa Sayıları: ss.93-100
  • Anahtar Kelimeler: Prostate cancer, toll-like receptors, flavonoid, nobiletin, inflammation, TOLL-LIKE RECEPTOR, SOLUBLE INTERLEUKIN-2-RECEPTOR, CITRUS NOBILETIN, ANGIOGENESIS, INFLAMMATION, EXPRESSION, SURVIVAL, INVASION
  • Kocaeli Üniversitesi Adresli: Evet

Özet

Background: Toll-like receptors (TLRs) are often expressed in natural immune cells as well as in tumor cells. TLR4 exhibits both tumor promoting and tumor-suppressing roles and higher TLR9 expression is an important marker of poor prognosis in prostate cancer (PCa). Nobiletin (NOB) is an O-methylated flavonoid and NOB has been proven to have anti-cancer effect in PCa cells. However, there is no study in the literature investigating the potential anti-inflammatory effects of NOB on the TLR signaling pathways in cancer. Therefore, we aimed to explore the potential anti-inflammatory effects of NOB on the TLR4/TRIF/IRF3 and TLR9/IRF7 signaling pathways in different types of PCa cell lines, for the first time. Material and methods: In the current study, the cytotoxic effect of NOB PC-3 (hormone-independent and metastatic) and LNCaP cells (hormone-dependent) was evaluated by WST-1 assay. Furthermore, the inhibitory effects of NOB on TLR4/TRIF/IRF3 and TLR9/IRF7signaling pathway were determined by RT-PCR, western blotting and ELISA analysis. Results: NOB demonstrated an inhibitory effect on PCa cell growth and LNCaP cells were more sensitive to NOB than PC-3 cells due to androjen receptor status. Furthermore, NOB alone could suppress TLR4/TRIF/IRF3 and TLR9/IRF7 signaling pathways through the downregulation of their associated pathways (mRNA and related protein levels) and the release of IFN-alpha and IFN-beta compared to LPS or CpG-ODN stimulated PCa cells. Conclusions: NOB potentially inhibited TLR4 and TL9-dependent signaling pathway in PCa cells. However, the efficacy of NOB was different in PCa cells due to the hormone status and aggressive features.