Interaction between dexamethasone and butyrate in apoptosis induction: non-additive in thymocytes and synergistic in a T cell-derived leukemia cell line.
In thymocytes butyrate and trichostatin A are unable to augment dexamethasone-induced apoptosis. In cultured rat thymocytes the extent of apoptosis induced by dexamethasone alone did not increase by addition of 0.1 - 10 mM butyrate. Even more pronounced was the non-additive interrelationship between dexamethasone and trichostatin A, as trichostatin A-induced apoptosis was not only blocked by the presence of dexamethasone but dexamethasone-induced apoptosis was also partially inhibited in the presence of 0.1 - 0.5 microM trichostatin A. The fact that the non-additive relationship with dexamethasone for apoptosis induction was observed with both histone deacetylase inhibitors suggests that in thymocytes this phenomenon is related to histone acetylation. In contrast to this, in the human T cell-derived leukemia cell line CEM-C7H2, dexamethasone did not block butyrate- or trichostatin A-induced apoptosis; moreover, butyrate, in the concentration range of 0.1 - 1 mM, had a marked synergistic effect on dexamethasone-induced apoptosis. This synergism, however, was not mimicked by trichostatin A, indicating that the effect is not related to histone acetylation but rather due to a pleiotropic effect of butyrate. Furthermore, in CEM-C7H2 cells, at higher concentrations of butyrate (5 - 10 mM) or trichostatin A (0.4 - 0.8 microM), there was a minor but reproducible antagonistic effect of dexamethasone on apoptosis induced by each of the two histone deacetylase inhibitors, suggesting that this antagonistic effect too, is related to histone hyperacetylation.
Bernhard
D
D
Institute of Medical Chemistry and Biochemistry, University of Innsbruck, Fritz-Pregl-Str. 3, A-6020 Innsbruck, Austria.
Löffler
M
M
Hartmann
B L
BL
Yoshida
M
M
Kofler
R
R
Csordas
A
A
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002087:Butyrates / Q000008:administration & dosage*; D002478:Cells, Cultured; D003907:Dexamethasone / Q000008:administration & dosage*; D004347:Drug Interactions; D004357:Drug Synergism; D006801:Humans; D006877:Hydroxamic Acids / Q000008:administration & dosage; D015458:Leukemia, T-Cell / Q000188:drug therapy / Q000473:pathology; D051381:Rats; D013601:T-Lymphocytes / Q000166:cytology* / Q000187:drug effects*; D014407:Tumor Cells, Cultured
D002087:Butyrates; D006877:Hydroxamic Acids; C012589:trichostatin A; D003907:Dexamethasone