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Histone deacetylase inhibitor sodium butyrate regulates the activation of toll-like receptor 4/interferon regulatory factor-3 signaling pathways in prostate cancer cells

1 Department of Medical Biology, Faculty of Medicine, Sakarya University, Sakarya, Turkey
2 Department of Medical Biology, Institute of Health Science, Sakarya University, Sakarya, Turkey
3 Department of Obstetrics and Gynecology, Faculty of Veterinary Medicine, Istanbul-Cerrahpasa University, Istanbul, Turkey

Correspondence Address:
Asuman Deveci Ozkan,
Department of Medical Biology, Faculty of Medicine, Sakarya University, Korucuk Campus, 54290, Sakarya
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jcrt.jcrt_2032_21

Context: The covalent acetylation and deacetylation of histone proteins by the histone deacetylase (HDAC) enzymes can be considered a novel therapeutic target in prostate cancer (PCa) cells. Sodium butyrate (NaBu) is a HDAC inhibitor (HDACi) which is a promising potential anticancer drug. Toll-like receptor 4 (TLR4) expression is increased in PCa cells and HDACi alter TLR-inducible gene expressions. Aims: We aimed to evaluate the effects of NaBu on TLR4 mediating signaling pathways in two different PCa cells (DU-145 and LNCaP) for the first time. Subjects and Methods: The cytotoxic and apoptotic effects of NaBu were determined by the water-soluble tetrazolium salt (WST-1) and Annexin V-AO/PI assays, respectively. Subcellular localization of TLR4, interferon regulatory factor-3 (IRF3) and Nuclear factor kappa B proteins was evaluated by IF assay. Statistical Analysis Used: All data were statistically analyzed by GraphPad Prism software (V60.1, CA). Obtained data were expressed in a mean ± standard deviation of the three repeated experiments. The differences between control and NaBu treated cells were compared by one-way-ANOVA. P < 0.05 value was considered statistically significant. Results: Our results showed that NaBu significantly inhibited the viability of PCa cells and increased the percentage of apoptotic cells. However, DU-145 cells were more sensitive to NaBu than LNCaP cells. Furthermore, NaBu can induce the cytoplasmic TLR4 and IRF3 expression in particularly DU-145 cells without affecting nuclear translocation of NF-kB in PCa cells. Conclusions: NaBu induces apoptotic cell death and regulated the TLR4/IRF3 signaling pathways in DU-145 cells but not in LNCaP cells. Therefore, PCa cells differentially responded to NaBu treatment due to probably androgen receptor status.

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