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

Deveci Ozkan, Asuman; Kaleli, Suleyman; Onen, Hacer Ilke; Sarihan, Mehmet; Guney Eskiler, Gamze; Kalayci Yigin, Aysel; Akdogan, Mehmet


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    "creators": [
      {
        "affiliation": "Sakarya Univ, Fac Med, Dept Med Biol, Sakarya, Turkey", 
        "name": "Deveci Ozkan, Asuman"
      }, 
      {
        "affiliation": "Sakarya Univ, Fac Med, Dept Med Biol, Sakarya, Turkey", 
        "name": "Kaleli, Suleyman"
      }, 
      {
        "affiliation": "Gazi Univ, Fac Med, Dept Med Biol, Ankara, Turkey", 
        "name": "Onen, Hacer Ilke"
      }, 
      {
        "affiliation": "Kocaeli Univ, Fac Med, Dept Med Biol, Kocaeli, Turkey", 
        "name": "Sarihan, Mehmet"
      }, 
      {
        "affiliation": "Sakarya Univ, Fac Med, Dept Med Biol, Sakarya, Turkey", 
        "name": "Guney Eskiler, Gamze"
      }, 
      {
        "affiliation": "Istanbul Univ, Cerrahpasa Med Fac, Dept Med Genet, Istanbul, Turkey", 
        "name": "Kalayci Yigin, Aysel"
      }, 
      {
        "affiliation": "Sakarya Univ, Fac Med, Dept Med Biochem, Sakarya, Turkey", 
        "name": "Akdogan, Mehmet"
      }
    ], 
    "description": "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.", 
    "doi": "10.1080/08923973.2020.1725040", 
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      "issue": "2", 
      "pages": "93-100", 
      "title": "IMMUNOPHARMACOLOGY AND IMMUNOTOXICOLOGY", 
      "volume": "42"
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    "title": "Anti-inflammatory effects of nobiletin on TLR4/TRIF/IRF3 and TLR9/IRF7 signaling pathways in prostate cancer cells"
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