Investigation of the effect of sodium butyrate induced differentiation on inflammatory pathways in colon cancer cells

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2012

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Küçükdemir, Mümine

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Sodium butyrate (NaBt) is a four-carbon short chain fatty acid, produced naturally in colon as the end product of the bacterial anaerobic metabolism on dietary fibers. It was previously shown that NaBt can induce differentiation and may inhibit proliferation. The objective of this study was to investigate the effect of NaBt-induced differentation on inflammatory pathways in HT29 colon cancer cells. For this purpose, first, cells were treated with varying concentrations of NaBt from 1-5 mM and amount required to induce differentiation was determined as 3 mM. To understand the effect of NaBt on inflammation, the NF-kappaB pathway (p50 and p65) was investigated. Immunofluorescent staining showed increased nuclear translocation of p50 subunit with no remarkable change in subcellular localization of p65; moreover a synergistic effect was observed when cells were co-treated with NaBt and an NF-kappaB repressor, Bay 11-7085; implying the formation of repressive p50 homodimers in the nucleus. Our preliminary chromatin immunoprecipitation results showed that p65 recruitment v to the promoters of ICAM-1 was reduced, whereas p50 recruitment was increased. However, analysis of NF-kappaB target genes showed that cells treated with 3 mM NaBt have higher expression of the cytokines IL1-β and TNF-α, adhesion molecules ICAM-1 and VCAM-1 but not COX-2. These results suggest that NaBt-induced differentiation could cause the emergence of an inflammatory signal in HT29 cells as an anti-tumor mechanism, independent from the NFkappaB activity. This work will be important in understanding the role of SCFAs in the colon microenvironment and may provide alternative therapeutic options in colorectal cancer.

Subject Keywords

Colon (Anatomy), Inflammatory bowel diseases., Anaerobic bacteria.

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http://etd.lib.metu.edu.tr/upload/12614490/index.pdf
https://hdl.handle.net/11511/21655

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Graduate School of Natural and Applied Sciences, Thesis

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Citation Formats

M. Küçükdemir, “Investigation of the effect of sodium butyrate induced differentiation on inflammatory pathways in colon cancer cells,” M.S. - Master of Science, Middle East Technical University, 2012.