XXXX exhibits biphasic effects on apoptotic cell death of activated lymphocytes through differential modulation of multiple signaling pathways.

@entity1380 @entity26490 @entity5 @entity19 @entity1092 @entity10433 @entity2052 @entity1379 @entity1995 @entity8837
@entity1092 ( @entity2052 ), a histone deacetylase (HDAC) inhibitor, possesses potent anti- @entity5 activity against a variety of malignant cells. However, its action on lymphocytes and the underlying mechanism are not completely understood. In this study, we aimed to analyze the effects of @entity2052 on the proliferation, activation, and apoptosis of @entity19 lymphocytes activated with concanavalin A (ConA). Our results showed that @entity2052 inhibited the proliferation of ConA-activated lymphocytes in a dose-dependent manner. Low-dose @entity2052 ( <= 1.1 mM) enhanced @entity26490 expression on the activated lymphocytes, whereas at high doses (>=  3.3 mM) it decreased @entity26490 expression. Furthermore, @entity2052 reduced activation-induced apoptotic cell death at low doses, but at high doses it promoted apoptotic cell death of activated lymphocytes dramatically. It was found that the @entity1380 / @entity1379 ratio and phosphorylation of histone H2A.X was decreased at low doses of @entity2052 but was increased at high doses. The phosphorylation of @entity10433 was also differentially regulated by different doses of @entity2052 . @entity2052 , at 5 mM induced the phosphorylation of @entity1995 but not JNK and @entity8837 . In addition, @entity2052 induced a dose-dependent increase in the acetylation of histone H3. These results demonstrate that @entity2052 exhibits dose-dependent biphasic effect on apoptosis of activated lymphocytes probably through differential modulation of several apoptosis-related signaling pathways.
