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Journal of Biomedicine and Biotechnology
Volume 2011, Article ID 197946, 14 pages
Review Article

Histone Deacetylase Inhibitors: The Epigenetic Therapeutics That Repress Hypoxia-Inducible Factors

Department of Biology and Graduate Program of Biological Sciences, College of Arts & Sciences, Drexel University, 3141 Chestnut Street, Stratton Hall 318, Philadelphia, PA 19104, USA

Received 20 July 2010; Accepted 25 September 2010

Academic Editor: Minoru Yoshida

Copyright © 2011 Shuyang Chen and Nianli Sang. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Histone deacetylase inhibitors (HDACIs) have been actively explored as a new generation of chemotherapeutics for cancers, generally known as epigenetic therapeutics. Recent findings indicate that several types of HDACIs repress angiogenesis, a process essential for tumor metabolism and progression. Accumulating evidence supports that this repression is mediated by disrupting the function of hypoxia-inducible factors (HIF-1, HIF-2, and collectively, HIF), which are the master regulators of angiogenesis and cellular adaptation to hypoxia. Since HIF also regulate glucose metabolism, cell survival, microenvironment remodeling, and other alterations commonly required for tumor progression, they are considered as novel targets for cancer chemotherapy. Though the precise biochemical mechanism underlying the HDACI-triggered repression of HIF function remains unclear, potential cellular factors that may link the inhibition of deacetylase activity to the repression of HIF function have been proposed. Here we review published data that inhibitors of type I/II HDACs repress HIF function by either reducing functional HIF-1α levels, or repressing HIF-α transactivation activity. In addition, underlying mechanisms and potential proteins involved in the repression will be discussed. A thorough understanding of HDACI-induced repression of HIF function may facilitate the development of future therapies to either repress or promote angiogenesis for cancer or chronic ischemic disorders, respectively.