Histone Deacetylase Inhibitors: An Attractive Therapeutic Strategy Against Breast Cancer

Damaskos, Christos; Valsami, Serena; Kontos, Michael C.; Spartalis, Eleftherios; Kalampokas, Theodoros; Kalampokas, Emmanouil; Athanasiou, Antonios; Moris, Demetrios; Daskalopoulou, Afrodite; Davakis, Spyridon; Tsourouflis, Gerasimos; Kontzoglou, Konstantinos; Perrea, Despina; Nikiteas, Nikolaos; Dimitroulis, Dimitrios

doi:10.21873/anticanres.11286

Cited by 164 publications

(159 citation statements)

References 90 publications

Supporting

Mentioning

151

Contrasting

Unclassified

Order By: Relevance

“…HDAC inhibitors, while increasingly studied as anti-cancer and anti-inflammatory agents [53], may also play a role in ictogenesis and/or epileptogenesis [54]. Valproic acid (VPA), a broad-spectrum anti-seizure drug in clinical use, has been shown to inhibit both class I and II HDACs and is cytotoxic to many different cancer types [55]. HDAC inhibition may be a key anti-seizure mechanism of VPA action, as prior studies had failed to provide a compelling explanation for a variety of methodological reasons [56, 57].…”

Section: Inhibition Of Histone Deacetylasesmentioning

confidence: 99%

Ketone Bodies as Anti-Seizure Agents

Simeone

Rho

2017

Neurochem Res

View full text Add to dashboard Cite

There is growing evidence that ketone bodies (KB)—derived from fatty acid oxidation and produced during fasting or consumption of high-fat diets—can exert broad neuroprotective effects. With respect to epilepsy, KB (such as β-hydroxybutyrate or BHB, acetoacetate and acetone) have been shown to block acutely induced and spontaneous recurrent seizures in various animal models. Although the mechanisms underlying the anti-seizure effects of KB have not been fully elucidated, recent experimental studies have invoked ketone-mediated effects on both inhibitory (e.g., GABAergic, purinergic and ATP-sensitive potassium channels) and excitatory (e.g., vesicular glutamate transporters) neurotransmission, as well as mitochondrial targets (e.g., respiratory chain and mitochondrial permeability transition). Moreover, BHB appears to exert both epigenetic (i.e., inhibition of histone deacetylases or HDACs) and anti-inflammatory (i.e., peripheral modulation of hydroxycarboxylic acid receptor and inhibition of the NOD-like receptor protein 3 or NRLP3 inflammasome) activity. While the latter two effects of BHB have yet to be directly linked to ictogenesis and/or epileptogenesis, parallel lines of evidence indicate that HDAC inhibition and a reduction in neuroinflammation alone or collectively can block seizure activity. Nevertheless, the notion that KB are themselves anti-seizure agents requires clinical validation, as prior studies have not revealed a clear correlation between blood ketone levels and seizure control. Notwithstanding this limitation, there is growing evidence that KB are more than just cellular fuels, and can exert profound biochemical, cellular and epigenetic changes favoring an overall attenuation in brain network excitability.

show abstract

Section: Inhibition Of Histone Deacetylasesmentioning

confidence: 99%

Ketone Bodies as Anti-Seizure Agents

Simeone

Rho

2017

Neurochem Res

View full text Add to dashboard Cite

show abstract

“…Chemotherapy using PARP or HDAC inhibitors is emerging as a novel therapeutic option to treat metastatic breast cancers, such as TNBC and tumors with BRCA mutations, by blocking DNA repair pathways while increasing the DNA damage burden of cells (29,30,31). Over half of patients with BRCAmutated, metastatic breast cancer have tumors classified as triple-negative, and clinical trials to assess the efficacy and safety of a TNKS inhibitor in metastatic TNBC patients are currently being conducted (32,33).…”

Section: Discussionmentioning

confidence: 99%

Combination Treatment of Polo-Like Kinase 1 and Tankyrase-1 Inhibitors Enhances Anticancer Effect in Triple-negative Breast Cancer Cells

2018

View full text Add to dashboard Cite

“…They are also known for their critical role in tumor development and malignancy (4,26,27). Although the anti-tumor effect of TSA has been demonstrated in some malignant tumors, these studies have focused on regulation of the cell cycle and apoptosis by TSA (26)(27)(28).…”

Section: Discussionmentioning

confidence: 99%

Trichostatin A Sensitizes Hepatocellular Carcinoma Cells to Enhanced NK Cell-mediated Killing by Regulating Immune-related Genes

Shin

Kim

Lee

et al. 2017

CGP

View full text Add to dashboard Cite

Abstract. Background Hepatocellular carcinoma (HCC) is the fifth most common malignancy and the second leading cause of death of cancer patients in the world (1). Although a lot of progress has been made in the clinical management of HCC, its prognosis still remains poor owing to high chances of metastasis and recurrence, leading to low overall survival (2). Treatment options for advanced HCC are extremely limited owing to the shortage of effective therapeutic agents. Currently, sorafanib is the only approved therapeutic agent for advanced HCC (3), so there is an urgent need for novel therapeutic drugs for this disease.Recently, epigenetic modulation of gene transcription through acetylation and deacetylation has been reported to play a role in the pathogenesis of advanced HCC (4-6). Specifically, histone deacetylases (HDAC)1-3 are upregulated in primary human HCC and the enhanced HDACs levels play a critical role in malignant growth and immune escape (7). Importantly, the deacetylation process is reversible and can be targeted by new drugs such as HDAC inhibitors (8, 9). Thus, the biology of HDACs in HCC makes the use of HDAC inhibitors to treat HCC an attractive option (9-11). HDAC inhibitors have been shown to have efficacy as anti-cancer agents in numerous phase I/II studies (http://www.clinicaltrials.gov), conducted in many different types of cancer (12,13).Trichostatin A (TSA) was originally discovered as an antifungal drug, but was later found to be a potent non-selective 349

show abstract

Histone Deacetylase Inhibitors: An Attractive Therapeutic Strategy Against Breast Cancer

Cited by 164 publications

References 90 publications

Ketone Bodies as Anti-Seizure Agents

Ketone Bodies as Anti-Seizure Agents

Combination Treatment of Polo-Like Kinase 1 and Tankyrase-1 Inhibitors Enhances Anticancer Effect in Triple-negative Breast Cancer Cells

Trichostatin A Sensitizes Hepatocellular Carcinoma Cells to Enhanced NK Cell-mediated Killing by Regulating Immune-related Genes

Contact Info

Product

Resources

About