The histone deacetylase enzymes remove acetyl groups from histone selleckchem MEK162 and non histone proteins, and lead to the formation of a compacted and transcriptionally repressed chromatin structure. As a result, the global gene expression profile is modified and cellular function is al tered via multiple pathways. Aberrant HDAC expression in cancers suggests that HDACs are potential targets for epigenetic treatment. Class 1 and 2 histone deacetylase expression in a panel of lymphoma cell lines and tissue sections was previously reported, and clinical evaluation indicates that lymph oid malignancies are more sensitive to HDAC inhibitors compared to other solid tumors. Accordingly, HDAC inhibitors have been widely used in clinical trials in lymph oma, including peripheral T cell lymphoma, mantle cell lymphoma, and DLBCL.

Furthermore, HDAC inhibi tors, e. g. Romidepsin and Vorinostat, have been accepted by the US FDA for treating advanced and refractory cutaneous T cell lymphoma. Although clinical trials have proven suppressing effects of selected inhibitors on DLBCL patients, no HDAC in hibitors have been approved for the treatment of DLBCL. Insights into the anti proliferative effects of HDAC inhibitors on DLBCL, and further understanding of the underlying mechanisms are of great importance. In this study, we evaluated the effects of Trichostatin A, a hydroxamic acid derivative that inhibits most HDAC isoforms, and elucidated the molecular mechanisms underlying the subsequent altered biological behavior of DLBCL cell lines.

We identified varied expression levels of HDACs in DoHH2, LY1 and LY8 cell lines, and thus we selected these lines for our investigation. Results Effects of TSA on growth inhibition in all three DLBCL cell lines induced by cell cycle arrest and apoptosis Three DLBCL cell lines were treated with varying concentrations of TSA. Growth of all three DLBCL cell lines was inhibited by TSA treatment in a dose dependent manner. A much higher drug concentration was needed to sig nificantly inhibit the growth of both LY1 and LY8 cells compared with DoHH2 cells. Probit Regression analysis of results after 48 h of TSA treatment revealed IC50 values for LY1, LY8 and DoHH2 cells of 250 nM, 350 nM and 45 nM, respectively, indicating DoHH2 cells as the most sensitive to TSA. From these results, we selected a treatment level for DoHH2 cells of 50 nM TSA, and 300 nM TSA for LY1 and LY8 cells for all subsequent experiments.

After 48 h treatment, the rela tive cell viability of DoHH2, LY1 and LY8 cells declined to 40%, 60% and 41%, respectively, and declined further to 21%, 19% and 6% after 72 Batimastat h treatment, indicating that TSA exhibits its inhibitory effects in DLBCL cells in a time dependent manner. We next examined the cell cycle phase distribution after TSA treatment. The percentage of untreated DoHH2 cells at G1 phase was 32. 73%, which increased to 59. 97% after 24 h TSA treatment, while the percent age of S phase cells decreased from 49.