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Am J Translational Res 2011;3(5):454-467
Review Article
Potential non-oncological applications of histone deacetylase inhibitors
Katherine Ververis, Tom C Karagiannis
Epigenomic Medicine, Baker IDI Heart and Diabetes Institute, The Alfred Medical Research and Education
Precinct, Melbourne, Victoria, Australia; Department of Pathology, The University of Melbourne, Parkville, Victoria,
Australia
Received September 15, 2011; accepted October 2, 2011; Epub October 10, 2011; Published October 31, 2011
Abstract: Histone deacetylase inhibitors have emerged as a new class of anticancer therapeutic drugs. Their
clinical utility in oncology stems from their intrinsic cytotoxic properties and combinatorial effects with other
conventional cancer therapies. To date, the histone deacetylase inhibitors suberoylanilide hydroxamic acid
(Vorinostat, Zolinza®) and depsipeptide (Romidepsin, Istodax®) have been approved by the US Food and Drug
Administration for the treatment of refractory cutaneous T-cell lymphoma. Further, there are currently over 100
clinical trials involving the use of histone deacetylase inhibitors in a wide range of solid and hematological
malignancies. The therapeutic potential of histone deacetylase inhibitors has also been investigated for
numerous other diseases. For example, the cytotoxic properties of histone deacetylase inhibitors are currently
being harnessed as a potential treatment for malaria, whereas the efficacy of these compounds for HIV relies on
de-silencing latent virus. The anti-inflammatory properties of histone deacetylase inhibitors are the predominant
mechanisms for other diseases, such as hepatitis, systemic lupus erythematosus and a wide range of
neurodegenerative conditions. Additionally, histone deacetylase inhibitors have been shown to be efficacious in
animal models of cardiac hypertrophy and asthma. Broad-spectrum histone deacetylase inhibitors are clinically
available and have been used almost exclusively in preclinical systems to date. However, it is emerging that
class- or isoform-specific compounds, which are becoming more readily available, may be more efficacious
particularly for non-oncological applications. The aim of this review is to provide an overview of the effects and
clinical potential of histone deacetylase inhibitors in various diseases. Apart from applications in oncology, the
discussion is focused on the potential efficacy of histone deacetylase inhibitors for the treatment of
neurodegenerative diseases, cardiac hypertrophy and asthma. (AJTR1109001).
Keywords: chromatin modifications, histone acetylation, histone deacetylase inhibitor, Trichostatin A,
neurodegeneration, cardiac hypertrophy, asthma
Full Text PDF
Address all correspondence to:
Dr. Tom Karagiannis
Epigenomic Medicine
BakerIDI Heart and Diabetes Institute
75 Commercial Road, Melbourne, VIC, Australia
Email: tom.karagiannis@bakeridi.edu.au
Phone: +613 8532 1309
Fax: +613 8532 1100
Review Article
Potential non-oncological applications of histone deacetylase inhibitors
Katherine Ververis, Tom C Karagiannis
Epigenomic Medicine, Baker IDI Heart and Diabetes Institute, The Alfred Medical Research and Education
Precinct, Melbourne, Victoria, Australia; Department of Pathology, The University of Melbourne, Parkville, Victoria,
Australia
Received September 15, 2011; accepted October 2, 2011; Epub October 10, 2011; Published October 31, 2011
Abstract: Histone deacetylase inhibitors have emerged as a new class of anticancer therapeutic drugs. Their
clinical utility in oncology stems from their intrinsic cytotoxic properties and combinatorial effects with other
conventional cancer therapies. To date, the histone deacetylase inhibitors suberoylanilide hydroxamic acid
(Vorinostat, Zolinza®) and depsipeptide (Romidepsin, Istodax®) have been approved by the US Food and Drug
Administration for the treatment of refractory cutaneous T-cell lymphoma. Further, there are currently over 100
clinical trials involving the use of histone deacetylase inhibitors in a wide range of solid and hematological
malignancies. The therapeutic potential of histone deacetylase inhibitors has also been investigated for
numerous other diseases. For example, the cytotoxic properties of histone deacetylase inhibitors are currently
being harnessed as a potential treatment for malaria, whereas the efficacy of these compounds for HIV relies on
de-silencing latent virus. The anti-inflammatory properties of histone deacetylase inhibitors are the predominant
mechanisms for other diseases, such as hepatitis, systemic lupus erythematosus and a wide range of
neurodegenerative conditions. Additionally, histone deacetylase inhibitors have been shown to be efficacious in
animal models of cardiac hypertrophy and asthma. Broad-spectrum histone deacetylase inhibitors are clinically
available and have been used almost exclusively in preclinical systems to date. However, it is emerging that
class- or isoform-specific compounds, which are becoming more readily available, may be more efficacious
particularly for non-oncological applications. The aim of this review is to provide an overview of the effects and
clinical potential of histone deacetylase inhibitors in various diseases. Apart from applications in oncology, the
discussion is focused on the potential efficacy of histone deacetylase inhibitors for the treatment of
neurodegenerative diseases, cardiac hypertrophy and asthma. (AJTR1109001).
Keywords: chromatin modifications, histone acetylation, histone deacetylase inhibitor, Trichostatin A,
neurodegeneration, cardiac hypertrophy, asthma
Full Text PDF
Address all correspondence to:
Dr. Tom Karagiannis
Epigenomic Medicine
BakerIDI Heart and Diabetes Institute
75 Commercial Road, Melbourne, VIC, Australia
Email: tom.karagiannis@bakeridi.edu.au
Phone: +613 8532 1309
Fax: +613 8532 1100
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