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

• Published in: Journal of cancer research and therapeutics Vol. 19; no. 7; pp. 1812 - 1817
• Main Authors: Ozkan, Asuman Deveci, Eskiler, Gamze Guney, Kazan, Nur, Turna, Ozge
• Format: Journal Article
• Language: English
• Published: India Wolters Kluwer - Medknow 01.10.2023; Medknow Publications and Media Pvt. Ltd; Medknow Publications & Media Pvt. Ltd
• Edition: 2
• Subjects: Apoptosis; Biological response modifiers; Cancer; Care and treatment; Development and progression; Drug therapy; Enzyme inhibitors; Esters; Gene expression; Genes; Health aspects; Histones; Interferon; Original Article; Physiological aspects; Prostate cancer; Sodium salts; TLR4; Transcription factors; Turkey; prostate cancer; sodium butyrate; toll-like receptor 4; Apoptosis
• ISSN: 0973-1482; 1998-4138; 1998-4138
• DOI: 10.4103/jcrt.jcrt_2032_21

ABSTRACT 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.