New Insights into the Connection Between Histone Deacetylases, Cell Metabolism, and Cancer

Chiaradonna, Ferdinando; Cirulli, Claudia; Palorini, Roberta; Votta, Giuseppina; Alberghina, Lilia

doi:10.1089/ars.2014.5854

Cited by 12 publications

(8 citation statements)

References 200 publications

(207 reference statements)

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“…Conversely, it has also been shown that metabolic intermediates may control HDAC activity in cancer cells 46 . This may represent a cross-talk connecting cell metabolism, transcription, and other HDACs-controlled processes in physiological and pathological conditions.…”

Section: Discussionmentioning

confidence: 99%

Metabolic and Proliferative State of Vascular Adventitial Fibroblasts in Pulmonary Hypertension Is Regulated Through a MicroRNA-124/PTBP1 (Polypyrimidine Tract Binding Protein 1)/Pyruvate Kinase Muscle Axis

Zhang¹,

Wang²,

Li³

et al. 2017

Circulation

189

194

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In PH, miR-124, through the alternative splicing factor PTBP1, regulates the PKM2/PKM1 ratio, the overall metabolic, proliferative, and inflammatory state of cells. This PH phenotype can be rescued with interventions at various levels of the metabolic cascade. These findings suggest a more integrated view of vascular cell metabolism, which may open unique therapeutic prospects in targeting the dynamic glycolytic and mitochondrial interactions and between mesenchymal inflammatory cells in PH.

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Section: Discussionmentioning

confidence: 99%

Metabolic and Proliferative State of Vascular Adventitial Fibroblasts in Pulmonary Hypertension Is Regulated Through a MicroRNA-124/PTBP1 (Polypyrimidine Tract Binding Protein 1)/Pyruvate Kinase Muscle Axis

Zhang¹,

Wang²,

Li³

et al. 2017

Circulation

189

194

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“…1,4 HDACs are important epigenetic markers that play a key role in modulating the expression of genes involved in cellular proliferation, apoptosis and differentiation. 5,6 As such, they represent an integrated target for cancer therapy, with the ineffectual metabolism of SCFA in cancer cells hypothesized to lead to an accumulation of acetyl-CoA in the nucleus, where it functions as an HDAC inhibitor. 7 Previous studies have attempted to target and disrupt the altered cellular metabolism in colonic cancer cells via supplementation with SCFA.…”

mentioning

confidence: 99%

Cationic lipid-based nanoparticles mediate functional delivery of acetate to tumor cells in vivo leading to significant anticancer effects

Brody¹,

Sahuri-Arisoylu²,

Parkinson³

et al. 2017

IJN

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Metabolic reengineering using nanoparticle delivery represents an innovative therapeutic approach to normalizing the deregulation of cellular metabolism underlying many diseases, including cancer. Here, we demonstrated a unique and novel application to the treatment of malignancy using a short-chain fatty acid (SCFA)-encapsulated lipid-based delivery system – liposome-encapsulated acetate nanoparticles for cancer applications (LITA-CAN). We assessed chronic in vivo administration of our nanoparticle in three separate murine models of colorectal cancer. We demonstrated a substantial reduction in tumor growth in the xenograft model of colorectal cancer cell lines HT-29, HCT-116 p53+/+ and HCT-116 p53−/−. Nanoparticle-induced reductions in histone deacetylase gene expression indicated a potential mechanism for these anti-proliferative effects. Together, these results indicated that LITA-CAN could be used as an effective direct or adjunct therapy to treat malignant transformation in vivo.

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“…HDAC class II is further subdivided into class IIa (HDACs 4, 5, 7, and 9) and class IIb (HDACs 6 and 8), with the latter being characterized as having two deacetylase domains [8]. Class IV has only one HDAC member (HDAC11) [11]. The classification and functions of HDACs are shown in Table 1.…”

Section: Classification Of Histone Deacetylasesmentioning

confidence: 99%

Role of Histone Deacetylases in Carcinogenesis: Potential Role in Cholangiocarcinoma

Pant

Peixoto

Richard

et al. 2020

Cells

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Cholangiocarcinoma (CCA) is a highly invasive and metastatic form of carcinoma with bleak prognosis due to limited therapies, frequent relapse, and chemotherapy resistance. There is an urgent need to identify the molecular regulators of CCA in order to develop novel therapeutics and advance diseases diagnosis. Many cellular proteins including histones may undergo a series of enzyme-mediated post-translational modifications including acetylation, methylation, phosphorylation, sumoylation, and crotonylation. Histone deacetylases (HDACs) play an important role in regulating epigenetic maintenance and modifications of their targets, which in turn exert critical impacts on chromatin structure, gene expression, and stability of proteins. As such, HDACs constitute a group of potential therapeutic targets for CCA. The aim of this review was to summarize the role that HDACs perform in regulating epigenetic changes, tumor development, and their potential as therapeutic targets for CCA.

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New Insights into the Connection Between Histone Deacetylases, Cell Metabolism, and Cancer

Abstract: High-throughput metabolic studies performed by using more sophisticated technologies applied to the available models of conditional deletion of HDACs in cell lines or in mice will fill the gap in the current understanding and open directions for future research.

Cited by 12 publications

References 200 publications

Metabolic and Proliferative State of Vascular Adventitial Fibroblasts in Pulmonary Hypertension Is Regulated Through a MicroRNA-124/PTBP1 (Polypyrimidine Tract Binding Protein 1)/Pyruvate Kinase Muscle Axis

Metabolic and Proliferative State of Vascular Adventitial Fibroblasts in Pulmonary Hypertension Is Regulated Through a MicroRNA-124/PTBP1 (Polypyrimidine Tract Binding Protein 1)/Pyruvate Kinase Muscle Axis

Cationic lipid-based nanoparticles mediate functional delivery of acetate to tumor cells in vivo leading to significant anticancer effects

Role of Histone Deacetylases in Carcinogenesis: Potential Role in Cholangiocarcinoma

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