Histone deacetylase in carcinogenesis and its inhibitors as anti-cancer agents

• Published in: BMB reports Vol. 36; no. 1; pp. 110 - 119
• Main Authors: Kim, Dong Hoon, Kim, Minjung, Kwon, Ho Jeong
• Format: Journal Article
• Language: English
• Published: Korea (South) 31.01.2003
• Subjects: Acetyltransferases - metabolism; Animals; Antineoplastic Agents - pharmacology; Cell Transformation, Neoplastic; Enzyme Inhibitors - pharmacology; Eukaryotic Cells; Gene Expression Regulation; Histone Acetyltransferases; Histone Deacetylase Inhibitors; Histone Deacetylases - chemistry; Histone Deacetylases - physiology; Humans; Neoplasms - drug therapy; Neoplasms - enzymology; Neovascularization, Pathologic; Promoter Regions, Genetic; Saccharomyces cerevisiae Proteins - metabolism; Substrate Specificity
• ISSN: 1225-8687; 1976-6696
• DOI: 10.5483/bmbrep.2003.36.1.110

The acetylation state of histone is reversibly regulated by histone acetyltransferase (HAT) and deacetylase (HDAC). An imbalance of this reaction leads to an aberrant behavior of the cells in morphology, cell cycle, differentiation, and carcinogenesis. Recently, these key enzymes in the gene expression were cloned. They revealed a broad use of this modification, not only in histone, but also other proteins that involved transcription, nuclear transport, and cytoskeleton. These results suggest that HAT/HDAC takes charge of multiple-functions in the cell, not just the gene expression. HDAC is especially known to play an important role in carcinogenesis. The enzyme has been considered a target molecule for cancer therapy. The inhibition of HDAC activity by a specific inhibitor induces growth arrest, differentiation, and apoptosis of transformed or several cancer cells. Some of these inhibitors are in a clinical trial at phase I or phase II. The discovery and development of specific HDAC inhibitors are helpful for cancer therapy, and decipher the molecular mode of action for HDAC.