Effects of histone deacetylase inhibitors on HIF-1.
Hypoxia inducible factors (HIF) are the master transcriptional regulators of angiogenesis and energy metabolism in mammals. Histone deacetylase inhibitors (HDAIs) are among the promising anti -cancer compounds currently in clinical trials. In addition to inducing hyperacetylation of histones, HDAIs have been found to repress HIF function, which has been construed as an important pharmacological mechanism underlying the HDAI -mediated repression of tumor growth and angiogenesis. While HDAIs are potent inhibitors of HIF function and thus may be useful in the prevention and treatment of cancers, a major dilemma is that they may induce hyperacetylation of nonspecific targets thus causing side effects. A better understanding is now required of the molecular and biochemical mechanisms underlying the anti -HIF effects of these compounds. Here we summarize the recent advances towards a better understanding of these molecular and biochemical mechanisms.
Liang
Dongming
D
Cardeza Foundation, Department of Medicine and Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
Kong
Xianguo
X
Sang
Nianli
N
D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D005786:Gene Expression Regulation; D056572:Histone Deacetylase Inhibitors; D006657:Histones / Q000378:metabolism*; D006801:Humans; D000860:Hypoxia; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D008954:Models, Biological; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D009389:Neovascularization, Pathologic; D010100:Oxygen / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation
D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D014157:Transcription Factors; D010100:Oxygen