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 dexamethaso ne-induced apoptosis, In cultured rat thymocytes the extent of apoptosis in duced by dexamethasone alone did not increase by addition of 0.1-10 mM buty rate, Even more pronounced was the non-additive interrelationship between d examethasone and trichostatin A, as trichostatin A-induced apoptosis was no t only blocked by the presence of dexamethasone but dexamethasone-induced a poptosis was also partially inhibited in the presence of 0.1-0.5 mu M trich ostatin A. The fact that the non-additive relationship with dexamethasone f or apoptosis induction was observed with both histone deacetylase inhibitor s suggests that in thymocytes this phenomenon is related to histone acetyla tion. In contrast to this, in the human T cell-derived leukemia cell line C EM-C7H2, dexamethasone did not block butyrate- or trichostatin A-induced ap optosis; moreover, butyrate, in the concentration range of 0.1-1 mM, had a marked synergistic effect on dexamethasone-induced apoptosis. This synergis m, however, was not mimicked by trichostatin A, indicating that the effect is not related to histone acetylation but rather due to a pleiotropic effec t of butyrate, Furthermore, in CEM-C7H2 cells, at higher concentrations of butyrate (5-10 mM) or trichostatin A (0.4-0.8 mu M), there was a minor but reproducible antagonistic effect of dexamethasone on apoptosis induced by e ach of the two histone deacetylase inhibitors, suggesting that this antagon istic effect too, is related to histone hyperacetylation.