STANDARD_NAME JOSEPH_RESPONSE_TO_SODIUM_BUTYRATE_DN SYSTEMATIC_NAME M1515 COLLECTION C2:CGP MSIGDB_URL https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/JOSEPH_RESPONSE_TO_SODIUM_BUTYRATE_DN NAMESPACE HUMAN_SEQ_ACCESSION DESCRIPTION_BRIEF Genes down-regulated in H460 cells (non-small cell lung carcinoma, NSCLC) after treatment with sodium butyrate [PubChem=5222465]. DESCRIPTION_FULL 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 gamma (IFNgamma) pathway. In good correlation, NaB-pretreated cells failed to induce interferon regulatory factor 1, an INFgamma target gene, efficiently upon IFNgamma 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. PMID 15318170 GEOID AUTHORS Joseph J,Mudduluru G,Antony S,Vashistha S,Ajitkumar P,Somasundaram K CONTRIBUTOR John Newman CONTRIBUTOR_ORG University of Washington EXACT_SOURCE Table 2 FILTERED_BY_SIMILARITY EXTERNAL_NAMES_FOR_SIMILAR_TERMS EXTERNAL_DETAILS_URL SOURCE_MEMBERS AA040255,AA042836,AA043457,AA088647,AA149475,AI668645,AI820764,AL046955,AW607760,BE738657,BG054547,BG675524,BG759096,BI493041,BM044542,BM049821,H25460,H27400,H28534,H30138,H48784,H58668,H75353,H79188,N31846,N34004,N34169,N41908,N77287,N95415,N98673,R01959,R02471,R18562,R23132,R23436,R23778,R23999,R47859,R48041,R67197,R73063,R74161,R81839,R88469,R90829,R94457,R96617,R99156,T81285,W17249,W24348,W24394,W25614,W31016,W33064,W38462,W38732,W39129,W44684,W47038,W56121,W84867,W92014 GENE_SYMBOLS COL6A3,IRF2,ZNF137P,,,MYL4,CD300C,FSTL1,CLCN3,NAMPT,RNF141,NCL,EIF4G2,TIMP3,CDK4,EMP3,CDH11,HMGB1,AQP1,THBS4,ALDH1A1,ELANE,ALAD,ERCC2,ACP2,STAT6,NF2,FES,F10,,GRM3,USP7,G6PC1,ATP7B,CUL1,PRKAR2A,C7,HSPG2,,GAA,THRA,CSF1,PYGL,TXK,DPP6,VEGFB,GMPS,ABCC2,CKS1B,PFKL,ELK3,IL11,A2M,THSD7A,IL6,TUBA4A,SULT1E1,AFF1,NUCB1,MPP3,ALPK2,CAPN7,CYP4A11,ADH6 FOUNDER_NAMES