Role of histone deacetylase inhibitors in the treatment of cancer (Review)

  • Authors:
    • Shaoping Mei
    • Anthony D. Ho
    • Ulrich Mahlknecht
  • View Affiliations

  • Published online on: December 1, 2004     https://doi.org/10.3892/ijo.25.6.1509
  • Pages: 1509-1519
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Abstract

Acetylation and deacetylation of nucleosomal histones play an important role in the modulation of chromatin structure, chromatin function and in the regulation of gene expression. Histone acetyltransferases (HATs) and histone deacetylases (HDACs) are two opposing classes of enzymes, which tightly control the equilibrium of histone acetylation. An imbalance in the equilibrium of histone acetylation has been associated with carcinogenesis and cancer progression. So far, a number of structurally distinct classes of compounds have been identified as HDAC inhibitors including the short-chain fatty acids, hydroxamates, cyclic tetrapeptides and benzamides. These compounds lead to an accumulation of acetylated histone proteins both in tumor cells and in normal tissues. HDAC inhibitors are able to activate differentiation, to arrest the cell cycle in G1 and/or G2, and to induce apoptosis in transformed or cancer cells. Attention is currently being drawn to molecular mechanisms involving histone deacetylases. An induction of p21WAF/CIP1 and a suppression of angiogenic stimulating factors have been observed in tumor cells following exposure to HDAC inhibitors. In xenograft models, several HDAC inhibitors have demonstrated antitumor activity with only few side effects. Several clinical trials showed that HDAC inhibitors in well tolerated doses have significant antitumoral activities. A combination of HDAC inhibitors with differentiation-inducing agents and cytotoxic drugs is an innovative therapeutic strategy that carries the potential for significant improvements in the treatment of cancer.

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December 2004
Volume 25 Issue 6

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Mei S, Ho AD and Mahlknecht U: Role of histone deacetylase inhibitors in the treatment of cancer (Review). Int J Oncol 25: 1509-1519, 2004
APA
Mei, S., Ho, A.D., & Mahlknecht, U. (2004). Role of histone deacetylase inhibitors in the treatment of cancer (Review). International Journal of Oncology, 25, 1509-1519. https://doi.org/10.3892/ijo.25.6.1509
MLA
Mei, S., Ho, A. D., Mahlknecht, U."Role of histone deacetylase inhibitors in the treatment of cancer (Review)". International Journal of Oncology 25.6 (2004): 1509-1519.
Chicago
Mei, S., Ho, A. D., Mahlknecht, U."Role of histone deacetylase inhibitors in the treatment of cancer (Review)". International Journal of Oncology 25, no. 6 (2004): 1509-1519. https://doi.org/10.3892/ijo.25.6.1509