The Interaction of Histone Deacetylase Inhibitors and DNA Methyltransferase Inhibitors in the Treatment of Human Cancer Cells

ISSN: 1875-5992 (Online)
ISSN: 1871-5206 (Print)

Volume 17, 14 Issues, 2017

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Anti-Cancer Agents in Medicinal Chemistry

Formerly: Current Medicinal Chemistry - Anti-Cancer Agents

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Michelle Prudhomme
Institut de Chimie de Clermont-Ferrand
Université Clermont Auvergne

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The Interaction of Histone Deacetylase Inhibitors and DNA Methyltransferase Inhibitors in the Treatment of Human Cancer Cells

Anti-Cancer Agents in Medicinal Chemistry, 3(3): 187-199.

Author(s): Wei-Guo Zhu and Gregory A Otterson.

Affiliation: The Ohio State University,Division of Hematology / Oncology, 1226 James Cancer Hospital and SoloveResearch Institute, 300 W, 10th Ave., Columbus, OH 43210, USA.


The potential anticancer activities of histone deacetylase (HDAC) inhibitors and DNA methyltransferase (DNMT) inhibitors have been extensively studied in recent years. HDAC inhibitors suppress the activities of multiple HDACs, leading to an increase in histone acetylation. This histone acetylation induces an enhancement of the expression of specific genes that elicit extensive cellular morphologic and metabolic changes, such as growth arrest, differentiation and apoptosis. DNMT inhibitors, such as 5-aza-cytidine (5-aza-CR) and 5-aza-2- deoxycytidine (5-aza-CdR) are also widely studied because DNA hypomethylation induces the re-activation of tumor suppressor genes that are silenced by methylation-mediated mechanisms. Recently, the combination of HDAC inhibitors or demethylating agents with other chemo-therapeutics has gained increasing interest as a possible molecularly targeted therapeutic strategy. In particular, the combination of HDAC inhibitors with demethylating agents has become attractive since histones are connected to DNA by both physical and functional interactions. To date, the accumulating evidence has confirmed the hypothesis that the combination of HDAC and DNMT inhibition is very effective (and synergistic) in inducing apoptosis, differentiation and / or cell growth arrest in human lung, breast, thoracic, leukemia and colon cancer cell lines. This review will discuss the in vitro effects of HDAC inhibitors, such as trichostatin A (TSA), sodium butyrate, depsipeptide (FR901228, FK228), valproic acid (VPA) and suberoylanilide hydroxamic acid (SAHA), and the demethylating agent, 5-aza-CdR used alone and in combination treatment of human cancer cells and the possible mechanisms involved.


histone deacetylase, histone acetylation, dna methyltransferase, deoxycytidine, transcriptional repression.

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Article Details

Volume: 3
Issue Number: 3
First Page: 187
Last Page: 199
Page Count: 13
DOI: 10.2174/1568011033482440
Price: $58

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