Asuman Deveci Ozkan, Gamze Guney Eskiler, Nur Kazan, Ozge Turna
{"title":"组蛋白去乙酰化酶抑制剂丁酸钠能调节前列腺癌细胞中 toll-like receptor 4/interferon regulatory factor-3 信号通路的激活。","authors":"Asuman Deveci Ozkan, Gamze Guney Eskiler, Nur Kazan, Ozge Turna","doi":"10.4103/jcrt.jcrt_2032_21","DOIUrl":null,"url":null,"abstract":"<p><strong>Context: </strong>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.</p><p><strong>Aims: </strong>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.</p><p><strong>Subjects and methods: </strong>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.</p><p><strong>Statistical analysis used: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":15208,"journal":{"name":"Journal of cancer research and therapeutics","volume":null,"pages":null},"PeriodicalIF":1.4000,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Histone deacetylase inhibitor sodium butyrate regulates the activation of toll-like receptor 4/interferon regulatory factor-3 signaling pathways in prostate cancer cells.\",\"authors\":\"Asuman Deveci Ozkan, Gamze Guney Eskiler, Nur Kazan, Ozge Turna\",\"doi\":\"10.4103/jcrt.jcrt_2032_21\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Context: </strong>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.</p><p><strong>Aims: </strong>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.</p><p><strong>Subjects and methods: </strong>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.</p><p><strong>Statistical analysis used: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>\",\"PeriodicalId\":15208,\"journal\":{\"name\":\"Journal of cancer research and therapeutics\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.4000,\"publicationDate\":\"2023-10-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of cancer research and therapeutics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.4103/jcrt.jcrt_2032_21\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2022/3/28 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q4\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of cancer research and therapeutics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.4103/jcrt.jcrt_2032_21","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2022/3/28 0:00:00","PubModel":"Epub","JCR":"Q4","JCRName":"ONCOLOGY","Score":null,"Total":0}
Histone deacetylase inhibitor sodium butyrate regulates the activation of toll-like receptor 4/interferon regulatory factor-3 signaling pathways in prostate cancer cells.
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.
期刊介绍:
The journal will cover technical and clinical studies related to health, ethical and social issues in field of Medical oncology, radiation oncology, medical imaging, radiation protection, non-ionising radiation, radiobiology. Articles with clinical interest and implications will be given preference.