The interaction of butyrate with TNF-alpha during differentiation and apoptosis of colon epithelial cells: role of NF-kappaB activation.
We demonstrated that TNF-alpha 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-alpha is a typical activator of NF-kappaB pathway, we studied the role of NF-kappaB activation in cell differentiation and death during the TNF-alpha and NaBt co-treatment. TNF-alpha induced rapid NF-kappaB 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-kappaB activity induced by TNF-alpha after 4h treatment. However, this initial potentiation of NF-kappaB activity was not observed in FHC cells. During additional time of TNF-alpha and NaBt co-treatment, NaBt decreased the TNF-alpha-mediated NF-kappaB activity in both cell types. We also detected a different response of HT-29 and FHC cells after the pre-treatment with the NF-kappaB inhibitor parthenolide. Our results indicated that NaBt-mediated differentiation and apoptosis of colon epithelial cells can be modulated by TNF-alpha. Furthermore, we found significant differences in the mechanism of the NaBt and TNF-alpha co-treatment effects between cells of non-cancer and cancer origin, suggesting that the NF-kappaB pathway may be more effectively involved in these processes in cancer cells.
Hýzd'alová
M
M
Department of Cytokinetics, Institute of Biophysics, Academy of Sciences of the Czech Republic, v.v.i., Královopolská 135, CZ-612 65 Brno, Czech Republic.
Hofmanová
J
J
Pacherník
J
J
Vaculová
A
A
Kozubík
A
A
D017209:Apoptosis / Q000187:drug effects*; D002087:Butyrates / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D003106:Colon / Q000166:cytology*; D004347:Drug Interactions; D019073:HT29 Cells; D006801:Humans; D016328:NF-kappa B / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D002087:Butyrates; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha