title: The effects of a histone deacetylase inhibitor on biological behavior of diffuse large B-cell lymphoma cell lines and insights into the underlying mechanisms.
abstract: BACKGROUND
  Epigenetic control using histone deacetylase (HDAC) inhibitors is a promising therapy for lymphomas. Insights into the anti-proliferative effects of HDAC inhibitors on diffuse large B-cell lymphoma (DLBCL) and further understanding of the underlying mechanisms, which remain unclear to date, are of great importance.
  
  
  METHODS
  Three DLBCL cell lines (DoHH2, LY1 and LY8) were used to define the potential epigenetic targets for Trichostatin A (TSA)-mediated anti-proliferative effects via CCK-8 assay. Cell cycle distribution and apoptosis were detected by flow cytometry. We further investigated the underlying molecular mechanisms by examining expression levels of relevant proteins using western blot analysis.
  
  
  RESULTS
  TSA treatment inhibited the growth of all three DLBCL cell lines and enhanced cell cycle arrest and apoptosis. Molecular analysis revealed upregulated acetylation of histone H3, α-tubulin and p53, and dephosphorylation of pAkt with altered expression of its main downstream effectors (p21, p27, cyclin D1 and Bcl-2). HDAC profiling revealed that all three cell lines had varying HDAC1-6 expression levels, with the highest expression of all six isoforms, in DoHH2 cells, which displayed the highest sensitivity to TSA.
  
  
  CONCLUSIONS
  Our results demonstrated that the HDAC inhibitor TSA inhibited DLBCL cell growth, and that cell lines with higher expression of HDACs tended to be more sensitive to TSA. Our data also suggested that inhibition of pAkt and activation of p53 pathway are the main molecular events involved in inhibitory effects of TSA.
authors.affiliation: Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, PR China. xyzhou100@yahoo.com.
authors.forename: Ying
authors.initials: Y
authors.lastname: Cai
authors.forename: Wenli
authors.initials: W
authors.lastname: Cui
authors.forename: Weixiang
authors.initials: W
authors.lastname: Chen
authors.forename: Ping
authors.initials: P
authors.lastname: Wei
authors.forename: Yayun
authors.initials: Y
authors.lastname: Chi
authors.forename: Ping
authors.initials: P
authors.lastname: Zhang
authors.forename: Rui
authors.initials: R
authors.lastname: Bi
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Zhou