Targeting histone deacetylase in cancer therapy

Hsiang Yu Lin, Chang-Shi Chen, Shuan Pei Lin, Jing Ru Weng, Ching Shih Chen

Research output: Contribution to journalReview article

197 Citations (Scopus)

Abstract

Histone deacetylase (HDAC) is recognized as one of the promising targets for cancer treatment as many HDAC inhibitors have entered clinical trials for both solid and liquid tumors. Nevertheless, the mechanisms underlying the antiproliferative effects of HDAC inhibitors remain elusive. Although they have been shown to regulate the transcription of a defined set of genes through chromatin remodeling, increasing evidence suggests that modifications of the epigenetic histone code may not be the primary mechanism for HDAC inhibitor-mediated growth inhibition and apoptosis in cancer cells. While histones still represent a primary target for the physiological function of HDACs, the antitumor effect of HDAC inhibitors might also be attributed to transcription-independent mechanisms by modulating the acetylation status of a series of nonhistone targets. Also noteworthy is the effect of HDAC inhibitors on Akt downregulation through the alteration of protein phosphatase 1 (PP1) complex formation. To provide an overview of the use of HDAC inhibitors in cancer treatment, this review addresses the following subjects: (1) the physiological relevance of HDAC-mediated acetylation of histone and nonhistone substrates, (2) the chemical biology of HDACs and development of a novel class of HDAC inhibitors, and (3) the protein acetylation-independent effect of HDAC inhibitors on the activation status of signaling kinases.

Original languageEnglish
Pages (from-to)397-413
Number of pages17
JournalMedicinal Research Reviews
Volume26
Issue number4
DOIs
Publication statusPublished - 2006 Jul 1

Fingerprint

Histone Deacetylase Inhibitors
Histone Deacetylases
Neoplasms
Acetylation
Therapeutics
Histones
Histone Code
Protein Phosphatase 1
Chromatin Assembly and Disassembly
Epigenomics
Phosphotransferases
Down-Regulation
Clinical Trials
Apoptosis
Growth

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmacology
  • Drug Discovery

Cite this

Lin, H. Y., Chen, C-S., Lin, S. P., Weng, J. R., & Chen, C. S. (2006). Targeting histone deacetylase in cancer therapy. Medicinal Research Reviews, 26(4), 397-413. https://doi.org/10.1002/med.20056
Lin, Hsiang Yu ; Chen, Chang-Shi ; Lin, Shuan Pei ; Weng, Jing Ru ; Chen, Ching Shih. / Targeting histone deacetylase in cancer therapy. In: Medicinal Research Reviews. 2006 ; Vol. 26, No. 4. pp. 397-413.
@article{b9ef29cf9ca1443ba76426ce6f1baea4,
title = "Targeting histone deacetylase in cancer therapy",
abstract = "Histone deacetylase (HDAC) is recognized as one of the promising targets for cancer treatment as many HDAC inhibitors have entered clinical trials for both solid and liquid tumors. Nevertheless, the mechanisms underlying the antiproliferative effects of HDAC inhibitors remain elusive. Although they have been shown to regulate the transcription of a defined set of genes through chromatin remodeling, increasing evidence suggests that modifications of the epigenetic histone code may not be the primary mechanism for HDAC inhibitor-mediated growth inhibition and apoptosis in cancer cells. While histones still represent a primary target for the physiological function of HDACs, the antitumor effect of HDAC inhibitors might also be attributed to transcription-independent mechanisms by modulating the acetylation status of a series of nonhistone targets. Also noteworthy is the effect of HDAC inhibitors on Akt downregulation through the alteration of protein phosphatase 1 (PP1) complex formation. To provide an overview of the use of HDAC inhibitors in cancer treatment, this review addresses the following subjects: (1) the physiological relevance of HDAC-mediated acetylation of histone and nonhistone substrates, (2) the chemical biology of HDACs and development of a novel class of HDAC inhibitors, and (3) the protein acetylation-independent effect of HDAC inhibitors on the activation status of signaling kinases.",
author = "Lin, {Hsiang Yu} and Chang-Shi Chen and Lin, {Shuan Pei} and Weng, {Jing Ru} and Chen, {Ching Shih}",
year = "2006",
month = "7",
day = "1",
doi = "10.1002/med.20056",
language = "English",
volume = "26",
pages = "397--413",
journal = "Medicinal Research Reviews",
issn = "0198-6325",
publisher = "John Wiley and Sons Inc.",
number = "4",

}

Lin, HY, Chen, C-S, Lin, SP, Weng, JR & Chen, CS 2006, 'Targeting histone deacetylase in cancer therapy', Medicinal Research Reviews, vol. 26, no. 4, pp. 397-413. https://doi.org/10.1002/med.20056

Targeting histone deacetylase in cancer therapy. / Lin, Hsiang Yu; Chen, Chang-Shi; Lin, Shuan Pei; Weng, Jing Ru; Chen, Ching Shih.

In: Medicinal Research Reviews, Vol. 26, No. 4, 01.07.2006, p. 397-413.

Research output: Contribution to journalReview article

TY - JOUR

T1 - Targeting histone deacetylase in cancer therapy

AU - Lin, Hsiang Yu

AU - Chen, Chang-Shi

AU - Lin, Shuan Pei

AU - Weng, Jing Ru

AU - Chen, Ching Shih

PY - 2006/7/1

Y1 - 2006/7/1

N2 - Histone deacetylase (HDAC) is recognized as one of the promising targets for cancer treatment as many HDAC inhibitors have entered clinical trials for both solid and liquid tumors. Nevertheless, the mechanisms underlying the antiproliferative effects of HDAC inhibitors remain elusive. Although they have been shown to regulate the transcription of a defined set of genes through chromatin remodeling, increasing evidence suggests that modifications of the epigenetic histone code may not be the primary mechanism for HDAC inhibitor-mediated growth inhibition and apoptosis in cancer cells. While histones still represent a primary target for the physiological function of HDACs, the antitumor effect of HDAC inhibitors might also be attributed to transcription-independent mechanisms by modulating the acetylation status of a series of nonhistone targets. Also noteworthy is the effect of HDAC inhibitors on Akt downregulation through the alteration of protein phosphatase 1 (PP1) complex formation. To provide an overview of the use of HDAC inhibitors in cancer treatment, this review addresses the following subjects: (1) the physiological relevance of HDAC-mediated acetylation of histone and nonhistone substrates, (2) the chemical biology of HDACs and development of a novel class of HDAC inhibitors, and (3) the protein acetylation-independent effect of HDAC inhibitors on the activation status of signaling kinases.

AB - Histone deacetylase (HDAC) is recognized as one of the promising targets for cancer treatment as many HDAC inhibitors have entered clinical trials for both solid and liquid tumors. Nevertheless, the mechanisms underlying the antiproliferative effects of HDAC inhibitors remain elusive. Although they have been shown to regulate the transcription of a defined set of genes through chromatin remodeling, increasing evidence suggests that modifications of the epigenetic histone code may not be the primary mechanism for HDAC inhibitor-mediated growth inhibition and apoptosis in cancer cells. While histones still represent a primary target for the physiological function of HDACs, the antitumor effect of HDAC inhibitors might also be attributed to transcription-independent mechanisms by modulating the acetylation status of a series of nonhistone targets. Also noteworthy is the effect of HDAC inhibitors on Akt downregulation through the alteration of protein phosphatase 1 (PP1) complex formation. To provide an overview of the use of HDAC inhibitors in cancer treatment, this review addresses the following subjects: (1) the physiological relevance of HDAC-mediated acetylation of histone and nonhistone substrates, (2) the chemical biology of HDACs and development of a novel class of HDAC inhibitors, and (3) the protein acetylation-independent effect of HDAC inhibitors on the activation status of signaling kinases.

UR - http://www.scopus.com/inward/record.url?scp=33745320974&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33745320974&partnerID=8YFLogxK

U2 - 10.1002/med.20056

DO - 10.1002/med.20056

M3 - Review article

C2 - 16450343

AN - SCOPUS:33745320974

VL - 26

SP - 397

EP - 413

JO - Medicinal Research Reviews

JF - Medicinal Research Reviews

SN - 0198-6325

IS - 4

ER -