Inhibition of histone deacetylase 2 increases apoptosis and p21Cip1/WAF1 expression, independent of histone deacetylase 1

Cell Death Differ. 2005 Apr;12(4):395-404. doi: 10.1038/sj.cdd.4401567.


Histone deacetylases (HDACs) 1 and 2 share a high degree of homology and coexist within the same protein complexes. Despite their close association, each possesses unique functions. We show that the upregulation of HDAC2 in colorectal cancer occurred early at the polyp stage, was more robust and occurred more frequently than HDAC1. Similarly, while the expression of HDACs1 and 2 were increased in cervical dysplasia and invasive carcinoma, HDAC2 expression showed a clear demarcation of high-intensity staining at the transition region of dysplasia compared to HDAC1. Upon HDAC2 knockdown, cells displayed an increased number of cellular extensions reminiscent of cell differentiation. There was also an increase in apoptosis, associated with increased p21Cip1/WAF1 expression that was independent of p53. These results suggest that HDACs, especially HDAC2, are important enzymes involved in the early events of carcinogenesis, making them candidate markers for tumor progression and targets for cancer therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / physiology*
  • Cell Cycle Proteins / metabolism*
  • Colorectal Neoplasms / metabolism
  • Cyclin-Dependent Kinase Inhibitor p21
  • Female
  • HeLa Cells
  • Histone Deacetylase 1
  • Histone Deacetylase 2
  • Histone Deacetylase Inhibitors*
  • Histone Deacetylases / genetics
  • Histone Deacetylases / metabolism*
  • Humans
  • Immunohistochemistry
  • RNA, Small Interfering
  • Repressor Proteins / antagonists & inhibitors*
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism
  • Uterine Cervical Dysplasia / metabolism
  • Uterine Cervical Dysplasia / pathology


  • CDKN1A protein, human
  • Cell Cycle Proteins
  • Cyclin-Dependent Kinase Inhibitor p21
  • Histone Deacetylase Inhibitors
  • RNA, Small Interfering
  • Repressor Proteins
  • HDAC1 protein, human
  • Histone Deacetylase 1
  • Histone Deacetylase 2
  • Histone Deacetylases