Histone deacetylase inhibitors: Biology and mechanism of action

被引:88
作者
Mehnert, Janice M. [1 ]
Kelly, Wm. Kevin [1 ]
机构
[1] Yale Canc Ctr, Dept Med Oncol, New Haven, CT 06520 USA
关键词
histone deacetylase; histone acetyltransferase; histone; deacetylase inhibitor; chromatin; epigenetics; transcription; apoptosis; angiogenesis;
D O I
10.1097/PPO.0b013e31803c72ba
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Histone deacetylases (HDACs) and histone acetyltransferases are enzymes that regulate chromatin structure and function through the removal and addition, respectively, of the acetyl group from the lysine residues of core nucleosomal histories. This post-translational modification of histories is an important process in the regulation of gene expression. Aberrant expression and recruitment and disrupted activities of HDACs and histone acetyltransferases have been found in malignant tissues, implicating their involvement in cancer. HDAC inhibitors (HDACIs) function through diverse mechanisms, including the promotion of cell cycle arrest and apoptosis and the inhibition of angiogenesis. Malignant cells appear more sensitive to the proapoptotic effects of HDACIs, underscoring the therapeutic potential of these agents. Multiple HDACIs are currently under investigation in clinical trials, including vorinostat (suberoylanilide hydroxamic acid), which was recently approved by the U.S. Food and Drug Administration for the treatment of cutaneous manifestations of cutaneous T-cell lymphoma in patients with progressive, persistent, or recurrent disease on or after 2 systemic therapies.
引用
收藏
页码:23 / 29
页数:7
相关论文
共 77 条
[1]  
ACHYRA MR, 2005, MOL PHARM, V68, P917
[2]   ETO, a target of t(8;21) in acute leukemia, makes distinct contacts with multiple histone deacetylases and binds mSin3A through its oligomerization domain [J].
Amann, JM ;
Nip, J ;
Strom, DK ;
Lutterbach, B ;
Harada, H ;
Lenny, N ;
Downing, JR ;
Meyers, S ;
Hiebert, SW .
MOLECULAR AND CELLULAR BIOLOGY, 2001, 21 (19) :6470-6483
[3]   It's about time: Scheduling alters effect of histone deacetylase inhibitors on camptothecin-treated cells [J].
Bevins, RL ;
Zimmer, SG .
CANCER RESEARCH, 2005, 65 (15) :6957-6966
[4]   Anticancer activities of histone deacetylase inhibitors [J].
Bolden, Jessica E. ;
Peart, Melissa J. ;
Johnstone, Ricky W. .
NATURE REVIEWS DRUG DISCOVERY, 2006, 5 (09) :769-784
[5]   The histone deacetylase inhibitor SAHA arrests cancer cell growth, up-regulates thioredoxin-binding protein-2, and down-regulates thioredoxin [J].
Butler, LM ;
Zhou, XB ;
Xu, WS ;
Scher, HI ;
Rifkind, RA ;
Marks, PA ;
Richon, VM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (18) :11700-11705
[6]  
Butler LM, 2000, CANCER RES, V60, P5165
[7]   Enhancement of in vitro and in vivo tumor cell radiosensitivity by valproic acid [J].
Camphausen, K ;
Cerna, D ;
Scott, T ;
Sproull, M ;
Burgan, WE ;
Cerra, MA ;
Fine, H ;
Tofilon, PJ .
INTERNATIONAL JOURNAL OF CANCER, 2005, 114 (03) :380-386
[8]   Modulation of radiation response by histone deacetylase inhibition [J].
Chinnaiyan, P ;
Vallabhaneni, G ;
Armstrong, E ;
Huang, SM ;
Harari, PM .
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 2005, 62 (01) :223-229
[9]  
Chobanian NH, 2004, ANTICANCER RES, V24, P539
[10]   Expression profile of histone deacetylase 1 in gastric cancer tissues [J].
Choi, JH ;
Kwon, HJ ;
Yoon, BI ;
Kim, JH ;
Han, SU ;
Joo, HJ ;
Kim, DY .
JAPANESE JOURNAL OF CANCER RESEARCH, 2001, 92 (12) :1300-1304