Histone deacetylase inhibitors for the treatment of cancer stem cells

MedChemComm ◽  
2016 ◽  
Vol 7 (12) ◽  
pp. 2217-2231 ◽  
Author(s):  
M. Dvorakova ◽  
T. Vanek
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Histone Deacetylase ◽  
Histone Deacetylase Inhibitors ◽  
Hdac Inhibitors ◽  
Epigenetic Drugs

HDAC inhibitors are a promising group of epigenetic drugs that show the ability to induce apoptosis in cancer stem cells.

Novel Histone Deacetylase Inhibitors Induce Growth Arrest, Apoptosis, and Differentiation in Sarcoma Cancer Stem Cells

2015 ◽  
Vol 58 (9) ◽  
pp. 4073-4079 ◽  
Author(s):  
Gemma Di Pompo ◽  
Manuela Salerno ◽  
Dante Rotili ◽  
Sergio Valente ◽  
Clemens Zwergel ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Histone Deacetylase ◽  
Histone Deacetylase Inhibitors ◽  
Growth Arrest ◽  
Induce Growth Arrest

scholarly journals Histone Deacetylase Inhibitors in Cell Pluripotency, Differentiation, and Reprogramming

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Androniki Kretsovali ◽  
Christiana Hadjimichael ◽  
Nikolaos Charmpilas
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Histone Deacetylase ◽  
Histone Deacetylase Inhibitors ◽  
Hdac Inhibitors ◽  
Ectopic Expression ◽  
Embryonic Stem ◽  
Induced Pluripotent Stem Cell ◽  
Stem Cell Differentiation ◽  
Induced Pluripotent

Histone deacetylase inhibitors (HDACi) are small molecules that have important and pleiotropic effects on cell homeostasis. Under distinct developmental conditions, they can promote either self-renewal or differentiation of embryonic stem cells. In addition, they can promote directed differentiation of embryonic and tissue-specific stem cells along the neuronal, cardiomyocytic, and hepatic lineages. They have been used to facilitate embryo development following somatic cell nuclear transfer and induced pluripotent stem cell derivation by ectopic expression of pluripotency factors. In the latter method, these molecules not only increase effectiveness, but can also render the induction independent of the oncogenes c-Myc and Klf4. Here we review the molecular pathways that are involved in the functions of HDAC inhibitors on stem cell differentiation and reprogramming of somatic cells into pluripotency. Deciphering the mechanisms of HDAC inhibitor actions is very important to enable their exploitation for efficient and simple tissue regeneration therapies.

scholarly journals Implication for Cancer Stem Cells in Solid Cancer Chemo-Resistance: Promising Therapeutic Strategies Based on the Use of HDAC Inhibitors.

2019 ◽  
Vol 8 (7) ◽  
pp. 912 ◽  
Author(s):  
Roca ◽  
Di Gennaro ◽  
Budillon
Keyword(s):  
Stem Cells ◽  
Drug Resistance ◽  
Cancer Stem Cells ◽  
Histone Deacetylase Inhibitors ◽  
Hdac Inhibitors ◽  
Therapeutic Strategies ◽  
The Cancer Genome Atlas ◽  
Solid Cancer ◽  
Differentiation Potential ◽  
Daunting Challenge

Resistance to therapy in patients with solid cancers represents a daunting challenge that must be addressed. Indeed, current strategies are still not effective in the majority of patients; which has resulted in the need for novel therapeutic approaches. Cancer stem cells (CSCs), a subset of tumor cells that possess self-renewal and multilineage differentiation potential, are known to be intrinsically resistant to anticancer treatments. In this review, we analyzed the implications for CSCs in drug resistance and described that multiple alterations in morphogenetic pathways (i.e. Hippo, Wnt, JAK/STAT, TGF-, Notch, Hedgehog pathways) were suggested to be critical for CSC plasticity. By interrogating The Cancer Genome Atlas (TCGA) datasets, we first analyzed the prevalence of morphogenetic pathways alterations in solid tumors with associated outcomes. Then, by highlighting epigenetic relevance in CSC development and maintenance, we selected histone deacetylase inhibitors (HDACi) as potential agents of interest to target this subpopulation based on the pleiotropic effects exerted specifically on altered morphogenetic pathways. In detail, we highlighted the role of HDACi in solid cancers and,specifically,in the CSC subpopulation and we pointed out some mechanisms by which HDACi are able to overcome drug resistance and to modulate stemness. Although, further clinical and preclinical investigations should be conducted to disclose the unclear mechanisms by which HDACi modulate several signaling pathways in different tumors. To date, several lines of evidence support the testing of novel combinatorial therapeutic strategies based on the combination of drugs commonly used in clinical practice and HDACi to improve therapeutic efficacy in solid cancer patients.

scholarly journals The Effect of Vicinal Difluorination on the Conformation and Potency of Histone Deacetylase Inhibitors

Molecules ◽  
2021 ◽  
Vol 26 (13) ◽  
pp. 3974
Author(s):  
A. Daryl Ariawan ◽  
Flora Mansour ◽  
Nicole Richardson ◽  
Mohan Bhadbhade ◽  
Junming Ho ◽  
...  
Keyword(s):  
Histone Deacetylase ◽  
Histone Deacetylase Inhibitors ◽  
Hdac Inhibitors ◽  
Molecular Conformations ◽  
Fluorinated Analogs ◽  
Selective Agents ◽  
Isoform Selectivity

Histone deacetylase enzymes (HDACs) are potential targets for the treatment of cancer and other diseases, but it is challenging to design isoform-selective agents. In this work, we created new analogs of two established but non-selective HDAC inhibitors. We decorated the central linker chains of the molecules with specifically positioned fluorine atoms in order to control the molecular conformations. The fluorinated analogs were screened against a panel of 11 HDAC isoforms, and minor differences in isoform selectivity patterns were observed.

scholarly journals Histone Deacetylase Inhibitors in the Treatment of Muscular Dystrophies: Epigenetic Drugs for Genetic Diseases

2011 ◽  
Vol 17 (5-6) ◽  
pp. 457-465 ◽  
Author(s):  
Silvia Consalvi ◽  
Valentina Saccone ◽  
Lorenzo Giordani ◽  
Giulia Minetti ◽  
Chiara Mozzetta ◽  
...  
Keyword(s):  
Histone Deacetylase ◽  
Histone Deacetylase Inhibitors ◽  
Genetic Diseases ◽  
Muscular Dystrophies ◽  
Epigenetic Drugs

scholarly journals Synergism of Heat Shock Protein 90 and Histone Deacetylase Inhibitors in Synovial Sarcoma

Sarcoma ◽  
2009 ◽  
Vol 2009 ◽  
pp. 1-10 ◽  
Author(s):  
Anne Nguyen ◽  
Le Su ◽  
Belinda Campbell ◽  
Neal M. Poulin ◽  
Torsten O. Nielsen
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Synovial Sarcoma ◽  
Histone Deacetylase ◽  
Histone Deacetylase Inhibitors ◽  
Hdac Inhibitors ◽  
Heat Shock Protein 90 ◽  
Hsp90 Inhibitor ◽  
Therapeutic Benefit ◽  
Multiple Time

Current systemic therapies have little curative benefit for synovial sarcoma. Histone deacetylase (HDAC) inhibitors and the heat shock protein 90 (Hsp90) inhibitor 17-AAG have recently been shown to inhibit synovial sarcoma in preclinical models. We tested combinations of 17-AAG with the HDAC inhibitor MS-275 for synergism by proliferation and apoptosis assays. The combination was found to be synergistic at multiple time points in two synovial sarcoma cell lines. Previous studies have shown that HDAC inhibitors not only induce cell death but also activate the survival pathway NF-κB, potentially limiting therapeutic benefit. As 17-AAG inhibits activators of NF-κB, we tested if 17-AAG synergizes with MS-275 through abrogating NF-κB activation. In our assays, adding 17-AAG blocks NF-κB activation by MS-275 and siRNA directed against histone deacetylase 3 (HDAC3) recapitulates the effects of MS-275. Additionally, we find that the NF-κB inhibitor BAY 11-7085 synergizes with MS-275. We conclude that agents inhibiting NF-κB synergize with HDAC inhibitors against synovial sarcoma.

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