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Sodium butyrate enhances STAT 1 expression in PLC/PRF/5 hepatoma cells and augments their responsiveness to interferon-α
Although interferon-α (IFN-α) has shown great promise in the treatment of chronic viral hepatitis, the anti-tumour effect of this agent in the therapy of liver cancer is unclear. Recent studies have demonstrated that differentiation-inducing agents could modulate the responsiveness of cancer cells t...
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Formato: | Texto |
Lenguaje: | English |
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Nature Publishing Group
1999
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2362280/ https://www.ncbi.nlm.nih.gov/pubmed/10360647 http://dx.doi.org/10.1038/sj.bjc.6690413 |
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author | Hung, W-C Chuang, L-Y |
author_facet | Hung, W-C Chuang, L-Y |
author_sort | Hung, W-C |
collection | PubMed |
description | Although interferon-α (IFN-α) has shown great promise in the treatment of chronic viral hepatitis, the anti-tumour effect of this agent in the therapy of liver cancer is unclear. Recent studies have demonstrated that differentiation-inducing agents could modulate the responsiveness of cancer cells to IFN-α by regulating the expression of signal transducers and activators of transcription (STAT) proteins, a group of transcription factors which play important roles in the IFN signalling pathway. We have reported that sodium butyrate is a potent differentiation inducer for human hepatoma cells. In this study, we investigated whether this drug could regulate the expression of STAT proteins and enhance the anti-tumour effect of IFN-α in hepatoma cells. We found that sodium butyrate specifically activated STAT1 gene expression and enhanced IFN-α-induced phosphorylation and activation of STAT1 proteins. Co-treatment with these two drugs led to G1 growth arrest, accompanied by down-regulation of cyclin D1 and up-regulation of p21(WAF-1), and accumulation of hypophosphorylated retinoblastoma protein in hepatoma cells. Additionally, internucleosomal DNA fragmentation, a biological hallmark of apoptosis, was detected in hepatoma cells after continuous incubation with a combination of these two drugs for 72 h. Our results show that sodium butyrate potently enhances the anti-tumour effect of IFN-α in vitro and suggest that a rational combination of these two drugs may be useful for the treatment of liver cancer. © 1999 Cancer Research Campaign |
format | Text |
id | pubmed-2362280 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 1999 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-23622802009-09-10 Sodium butyrate enhances STAT 1 expression in PLC/PRF/5 hepatoma cells and augments their responsiveness to interferon-α Hung, W-C Chuang, L-Y Br J Cancer Regular Article Although interferon-α (IFN-α) has shown great promise in the treatment of chronic viral hepatitis, the anti-tumour effect of this agent in the therapy of liver cancer is unclear. Recent studies have demonstrated that differentiation-inducing agents could modulate the responsiveness of cancer cells to IFN-α by regulating the expression of signal transducers and activators of transcription (STAT) proteins, a group of transcription factors which play important roles in the IFN signalling pathway. We have reported that sodium butyrate is a potent differentiation inducer for human hepatoma cells. In this study, we investigated whether this drug could regulate the expression of STAT proteins and enhance the anti-tumour effect of IFN-α in hepatoma cells. We found that sodium butyrate specifically activated STAT1 gene expression and enhanced IFN-α-induced phosphorylation and activation of STAT1 proteins. Co-treatment with these two drugs led to G1 growth arrest, accompanied by down-regulation of cyclin D1 and up-regulation of p21(WAF-1), and accumulation of hypophosphorylated retinoblastoma protein in hepatoma cells. Additionally, internucleosomal DNA fragmentation, a biological hallmark of apoptosis, was detected in hepatoma cells after continuous incubation with a combination of these two drugs for 72 h. Our results show that sodium butyrate potently enhances the anti-tumour effect of IFN-α in vitro and suggest that a rational combination of these two drugs may be useful for the treatment of liver cancer. © 1999 Cancer Research Campaign Nature Publishing Group 1999-05 /pmc/articles/PMC2362280/ /pubmed/10360647 http://dx.doi.org/10.1038/sj.bjc.6690413 Text en Copyright © 1999 Cancer Research Campaign https://creativecommons.org/licenses/by/4.0/This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material.If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Regular Article Hung, W-C Chuang, L-Y Sodium butyrate enhances STAT 1 expression in PLC/PRF/5 hepatoma cells and augments their responsiveness to interferon-α |
title | Sodium butyrate enhances STAT 1 expression in PLC/PRF/5 hepatoma cells and augments their responsiveness to interferon-α |
title_full | Sodium butyrate enhances STAT 1 expression in PLC/PRF/5 hepatoma cells and augments their responsiveness to interferon-α |
title_fullStr | Sodium butyrate enhances STAT 1 expression in PLC/PRF/5 hepatoma cells and augments their responsiveness to interferon-α |
title_full_unstemmed | Sodium butyrate enhances STAT 1 expression in PLC/PRF/5 hepatoma cells and augments their responsiveness to interferon-α |
title_short | Sodium butyrate enhances STAT 1 expression in PLC/PRF/5 hepatoma cells and augments their responsiveness to interferon-α |
title_sort | sodium butyrate enhances stat 1 expression in plc/prf/5 hepatoma cells and augments their responsiveness to interferon-α |
topic | Regular Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2362280/ https://www.ncbi.nlm.nih.gov/pubmed/10360647 http://dx.doi.org/10.1038/sj.bjc.6690413 |
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