The interaction of butyrate with TNF-α during differentiation and apoptosis of colon epithelial cells: Role of NF-κB activation

Abstract

We demonstrated that TNF-α suppressed differentiation and potentiated cell death induced by butyrate (NaBt) in both adenocarcinoma HT-29 and fetal FHC human colon cells in vitro. Since TNF-α is a typical activator of NF-κB pathway, we studied the role of NF-κB activation in cell differentiation and death during the TNF-α and NaBt co-treatment. TNF-α induced rapid NF-κB activation in both HT-29 and FHC cell lines and this effect was differently modulated by NaBt in these two cell lines. In HT-29 cells, NaBt potentiated NF-κB activity induced by TNF-α after 4 h treatment. However, this initial potentiation of NF-κB activity was not observed in FHC cells. During additional time of TNF-α and NaBt co-treatment, NaBt decreased the TNF-α-mediated NF-κB activity in both cell types. We also detected a different response of HT-29 and FHC cells after the pre-treatment with the NF-κB inhibitor parthenolide. Our results indicated that NaBt-mediated differentiation and apoptosis of colon epithelial cells can be modulated by TNF-α. Furthermore, we found significant differences in the mechanism of the NaBt and TNF-α co-treatment effects between cells of non-cancer and cancer origin, suggesting that the NF-κB pathway may be more effectively involved in these processes in cancer cells.