Histone deacetylases function as novel potential therapeutic targets for cancer

Diverse cellular functions, including tumor suppressor gene expression, DNA repair, cell proliferation and apoptosis, are regulated by histone acetylation and deacetylation. Histone deacetylases (HDACs) are enzymes involved in remodeling of chromatin by deacetylating the lysine residues. They play a pivotal role in epigenetic regulation of gene expression. Dysregulation of HDACs and aberrant chromatin acetylation and deacetylation have been implicated in the pathogenesis of various diseases, including cancer. Histone deacetylases have become a target for the development of drugs for treating cancer because of their major contribution to oncogenic cell transformation. Overexpression of HDACs correlates with tumorigenesis. Previous work showed that inhibition of HDACs results in apoptosis and the inhibition of cell proliferation in multiple cells. A significant number of HDAC inhibitors have been developed in the past decade. These inhibitors have strong anticancer effects in vitro and in vivo, inducing growth arrest, differentiation, and programmed cell death, inhibiting cell migration, invasion, and metastasis, and suppressing angiogenesis. In addition, HDAC-mediated deacetylation alters the transcriptional activity of nuclear transcription factors, including p53, E2F, c-Myc, and nuclear factor-κB, as well as the extracellular signal-regulated kinase1/2, phosphatidylinositol 3-kinase, Notch, and Wnt signaling pathways. This review highlights the role of HDACs in cancer pathogenesis and, more importantly, that HDACs are potential novel therapeutic targets.