Expression proﬁling of sodium butyrate (NaB)-treated cells: identiﬁcation of regulation of genes related to cytokine signaling and cancer metastasis by NaB
Joseph, Jeena and Mudduluru, Giridhar and Antony, Sini and Vashistha, Surabhi and Ajitkumar, Parthasarathi and Somasundaram, Kumaravel (2004) Expression proﬁling of sodium butyrate (NaB)-treated cells: identiﬁcation of regulation of genes related to cytokine signaling and cancer metastasis by NaB. Oncogene 23(37):pp. 6304-6315.
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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 NaBtreated 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 NaBtreated cells revealed the downregulation of a total of 16 genes associated with cytokine signaling, in particular, interferon c (IFNc) pathway. In good correlation, NaBpretreated cells failed to induce interferon regulatory factor 1, an INFc target gene, efﬁciently upon IFNc addition. These results suggest that NaB inhibits proin- ﬂammatory 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 antiinvasive properties of NaB. Therefore, our study presents new evidence for pathways regulated by NaB, thus providing evidence for the mechanism behind antiinﬂammatory and antimetastatic activities of NaB.
Item Type: Journal Article
Keywords: Sodium butyrate;histone deacetyalse inhibitor;chromatin remodeling;microarray;expression proﬁling;cytokine signaling;metastasis
Department/Centre: Division of Biological Sciences > Microbiology & Cell Biology
ID Code: 2122
Deposited By: Swamy, Nanjunda M
Deposited On: 29 November 2004
Additional Information: Copyright for this article belongs to Nature Publishing Group.
Alternative Locations: http://www.nature.com/cgi-taf/DynaPage.taf?file=/onc/journal/v23/n37/full/1207852a.html&filetype=PDF