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-&beta / and TNF-&alpha / , 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.
| Identifer | oai:union.ndltd.org:METU/oai:etd.lib.metu.edu.tr:http://etd.lib.metu.edu.tr/upload/12614490/index.pdf |
| Date | 01 July 2012 |
| Creators | Kucukdemir, Mumine |
| Contributors | Banerjee, Sreeparna |
| Publisher | METU |
| Source Sets | Middle East Technical Univ. |
| Language | English |
| Detected Language | English |
| Type | M.S. Thesis |
| Format | text/pdf |
| Rights | Access forbidden for 1 year |
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