Evaluation of the Effects of Nobiletin on Toll-Like Receptor 3 Signaling Pathways in Prostate Cancer In Vitro

Abstract

Nobiletin as a nontoxic dietary citrus flavonoid has anticancer effects in cancer. Toll-like receptor three has a role in prostate cancer progression. However the relationship among NOB and TLR3 signaling in PCa has not been elucidated, yet. Therefore, we aimed to evaluate the effects of NOB on the activation of TLR3 signaling pathways in PCa In Vitro. PC-3, LNCaP and HUVEC cells were used for comparison of NOB-mediated TLR3 signaling pathways. After treatment with NOB and Poly I:C alone and NOB + Poly I:C, RT-PCR, western blotting and ELISA assay were performed to evaluate changes in gene and protein expression level, as well as CASP8. NOB potentially induced TLR3/IRF3 signaling pathway and the activation of TLR3/IRF3 signaling pathway by both NOB and Poly I:C was more profound in LNCaP than PC-3 cells. However, the level of TRIF protein and CASP8 decreased after both NOB and Poly I:C incubation. NOB could mediate TLR3 signaling pathways. NOB + Poly I:C could improve the activation of TLR3/IRF3 signaling pathway. However, the activation of TRIF/RIPK1/FADD signaling pathway reduced. Therefore, the elucidation of molecular mechanisms of TLR3 signaling pathways and the combination effects of NOB + Poly I:C on apoptotic cell death are further studied.

Acknowledgments

The authors thank Prof. Dr. Murat Kasap and Assoc. Prof. Dr. Gurler Akpinar from the Department of Medical Biology, Kocaeli University and Assoc. Prof. Dr. Ozlem Aksoy from the Department of Biology, Kocaeli University for support of our experiments.

Author’s Contributions

ADO, MS and SK conceived and designed research. ADO and SK conducted experiments. SK analyzed data. ADO and MS wrote the manuscript. All authors read carefully and approved the manuscript.

Disclosure Statement

The authors declare no competing financial interest.

Additional information

Funding

This study was supported by the Scientific Research Projects Foundation (BAP) of the Sakarya University of Turkey [Project No: 2016-08-06-031].