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  • Oncogenomics
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Expression profiling of sodium butyrate (NaB)-treated cells: identification of regulation of genes related to cytokine signaling and cancer metastasis by NaB

Oncogene volume 23, pages 6304–6315 (2004)Cite this article

Abstract

Histone deacetylase (HDAC) inhibitors induce growth arrest and apoptosis in a variety of human cancer cells. Sodium butyrate (NaB), a short chain fatty acid, is a HDAC inhibitor and is produced in the colonic lumen as a consequence of microbial degradation of dietary fibers. In order to dissect out the mechanism of NaB-induced growth inhibition of cancer cells, we carried out expression profiling of a human lung carcinoma cell line (H460) treated with NaB using a cDNA microarray. Of the total 1728 genes analysed, there were 32 genes with a mean expression value of 2.0-fold and higher and 66 genes with a mean expression value 3.0-fold and lower in NaB-treated cells. For a few selected genes, we demonstrate that their expression pattern by semiquantitative reverse transcription–polymerase chain reaction (RT–PCR) analysis is matching with the results obtained by microarray analysis. Closer view at the expression profile of NaB-treated cells revealed the downregulation of a total of 16 genes associated with cytokine signaling, in particular, interferon γ (IFNγ) pathway. In good correlation, NaB-pretreated cells failed to induce interferon regulatory factor 1, an INFγ target gene, efficiently upon IFNγ addition. These results suggest that NaB inhibits proinflammatory cytokine signaling pathway, thus providing proof of mechanism for its anti-inflammatory activity. We also found that NaB induced three genes, which are known metastatic suppressors, and downregulated 11 genes, which have been shown to promote metastasis. Upregulation of metastatic suppressor Kangai 1 (KAI1) by NaB in a time-dependent manner was confirmed by RT–PCR analysis. The differential regulation of metastasis-associated genes by NaB provides explanation for the anti-invasive properties of NaB. Therefore, our study presents new evidence for pathways regulated by NaB, thus providing evidence for the mechanism behind anti-inflammatory and antimetastatic activities of NaB.

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Abbreviations

NaB, sodium butyrate∣IFNγ, interferon gamma∣IRF1:

interferon regulatory factor 1

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Acknowledgements

This study was supported partly by funding from Indian Council of Medical Research, Government of India, ICMR Center for Advanced Study in Molecular Medical Microbiology and Department of Biotechnology, Government of India, as Program support. JJ is supported by a postdoctoral fellowship from Department of Biotechnology (DBT).

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  1. Jeena Joseph and Giridhar Mudduluru: These authors contributed equally to this work

Authors and Affiliations

  1. Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, 560 012, India

    Jeena Joseph, Giridhar Mudduluru, Sini Antony, Surabhi Vashistha, Parthasarathi Ajitkumar & Kumaravel Somasundaram

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  1. Jeena Joseph
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Correspondence to Kumaravel Somasundaram.

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Joseph, J., Mudduluru, G., Antony, S. et al. Expression profiling of sodium butyrate (NaB)-treated cells: identification of regulation of genes related to cytokine signaling and cancer metastasis by NaB. Oncogene 23, 6304–6315 (2004). https://doi.org/10.1038/sj.onc.1207852

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