Butyrate-enhanced TNFalpha-induced apoptosis is associated with inhibition of NF-kappaB.
BACKGROUND
Tumor necrosis factor (TNFalpha)-induced apoptosis is limited by concomitant activation of nuclear factor kappa B (NF-kappaB)-dependent anti-apoptotic genes. Butyrate inhibits NF-kappaB activation so that co-treatment with butyrate effectively enhances TNFalpha-induced apoptosis. In this context, the inhibition of NF-kappaB activation and subsequent modulation of (NF-kappaB)-dependent genes was assessed


METHODS
Human colon adenocarcinoma cells (SW620) were incubated with TNFalpha and butyrate. Apoptosis was determined by annexin V/propidium iodide staining and flow cytometry. NF-kappaB activation was detected by electrophoretic mobility shift assay. The expression of NF-kappaB-dependent genes was assessed by RNase protection assay (RPA) RESULTS: The TNFalpha/butyrate combination yielded an additive increase in the number of apoptotic cells. NF-kappaB nuclear translocation was successfully inhibited by co-incubation with butyrate. However, the expression pattern of NF-kappaB-dependent genes remained essentially unchanged


CONCLUSIONS
Butyrate enhances TNFalpha-induced apoptosis in the human adenocarcinoma cell line SW620. This additive effect may, at least in part, be mediated by the inhibition of NF-kappaB activation, presumably by impairing the anti-apoptotic properties of NF-kappaB.
Lührs
Hardi
H
Department of Medicine, University of Würzburg, Germany. h.luehrs@medizin.uni-wuerzburg.de
Kudlich
Theodor
T
Neumann
Manfred
M
Schauber
Jürgen
J
Melcher
Ralph
R
Gostner
Andrea
A
Scheppach
Wolfgang
W
Menzel
Thomas P
TP
D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002087:Butyrates / Q000494:pharmacology*; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005434:Flow Cytometry; D006801:Humans; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000502:physiology; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D002087:Butyrates; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha