Inhibition of histone deacetylase 4 increases cytotoxicity of docetaxel in gastric cancer cells

Colarossi, Lorenzo; Memeo, Lorenzo; Colarossi, Cristina; Aiello, Eleonora; Iuppa, A; Espina, Virginia; Liotta, Lance A.; Mueller, Claudius

doi:10.1002/prca.201400058

Cited by 23 publications

(15 citation statements)

References 36 publications

(50 reference statements)

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“…22,23 HDAC4, a member of the HDAC family, is overexpressed in GC, and plays multiple roles in the malignant characteristics of GC cells in vitro and in vivo. [33][34][35] Understanding the newly identified RGMB-AS1-miR-574-HDAC4 regulatory network can clarify the oncogenic activities of RGMB-AS1 in GC and may point to promising therapeutic regimens for patients with GC.…”

Section: Discussionmentioning

confidence: 99%

Long Noncoding RNA RGMB-AS1 Acts as a microRNA-574 Sponge Thereby Enhancing the Aggressiveness of Gastric Cancer via HDAC4 Upregulation

Wang¹,

Chen²,

Tian³

et al. 2020

OTT

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Purpose: The long noncoding RNA RGMB-AS1 plays an important part in the genesis and progression of multiple human cancers. Nonetheless, little is known regarding its expression, roles, and mechanisms of action in gastric cancer (GC). This study was aimed at investigating the relationship between RGMB-AS1 and GC and illustrating the mechanisms of action of RGMB-AS1 therein. Methods: RGMB-AS1 expression in GC was measured via reverse-transcription quantitative PCR. A series of experiments including Cell Counting Kit-8 assay, flow-cytometric analysis of apoptosis, Transwell migration and invasion assays, and in vivo tumorigenesis experiment were conducted to test the effects of RGMB-AS1 on the malignant phenotype of GC cells. The molecular events behind the oncogenic actions of RGMB-AS1 in GC were elucidated through subcellular fractionation, RNA immunoprecipitation assay, bioinformatics analysis and luciferase reporter assay. Results: RGMB-AS1 upregulation was confirmed in GC tissues and cell lines. Higher RGMB-AS1 expression was associated with adverse clinical parameters and negatively correlated with patient overall survival. RGMB-AS1 knockdown inhibited GC cell proliferation, facilitated apoptosis, and reduced migration and invasion in vitro. Further experiments revealed that RGMB-AS1 knockdown decreased the tumor growth of GC cells in vivo. Mechanistically, RGMB-AS1 functioned as a competing endogenous RNA upregulating histone deacetylase 4 (HDAC4) by sponging . Rescue experiments indicated that miR-574 inhibition and HDAC4 reintroduction reversed the effects of the RGMB-AS1 knockdown on GC cells. Conclusion: The RGMB-AS1-miR-574-HDAC4 regulatory network contributes to the malignancy of GC, thereby offering a novel target for the diagnosis, prognosis, and/or treatment of GC.

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Section: Discussionmentioning

confidence: 99%

Long Noncoding RNA RGMB-AS1 Acts as a microRNA-574 Sponge Thereby Enhancing the Aggressiveness of Gastric Cancer via HDAC4 Upregulation

Wang¹,

Chen²,

Tian³

et al. 2020

OTT

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“…The additional treatment with MC1568 to simvastatin led to further induction of p27 expression and displayed a considerable synergistic anti-proliferative effect in colorectal cancer cells (Ishikawa et al 2014). MC1568 also had a synergistic effect with docetaxel treatment to increase cytotoxicity in gastric cancer cells (Colarossi et al 2014). …”

Section: Anticancer Effect Of Hdac Inhibitorsmentioning

confidence: 99%

HDACs and HDAC Inhibitors in Cancer Development and Therapy

Seto

2016

Cold Spring Harb Perspect Med

961

765

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Over the last several decades, it has become clear that epigenetic abnormalities may be one of the hallmarks of cancer. Post-translational modifications of histones, for example, may play a crucial role in cancer development and progression by modulating gene transcription, chromatin remodeling and nuclear architecture. Histone acetylation, a well-studied post-translational histone modification, is controlled by the opposing activities of histone acetyltransferases (HATs) and histone deacetylases (HDACs). By removing acetyl groups, HDACs reverse chromatin acetylation and alter transcription of oncogenes and tumor suppressor genes. In addition, HDACs deacetylate numerous non-histone cellular substrates that govern a wide array of biological processes including cancer initiation and progression. This review will discuss the role of HDACs in cancer and the therapeutic potential of HDAC inhibitors (HDACi) as emerging drugs in cancer treatment.

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“…The search for isoform specific HDAC inhibitors is a current topic in drug discovery, given that individual isoforms have been linked to distinct pathological processes [7][8][9][10][11][12][13] . Some isoformspecific inhibitors were shown to be less toxic compared to pan-HDAC inhibitors 14,15 .…”

Section: Introductionmentioning

confidence: 99%

Cell-based multi-substrate assay coupled to UHPLC-ESI-MS/MS for a quick identification of class-specific HDAC inhibitors

Zwick

Simões-Pires

Cuendet

2016

Journal of Enzyme Inhibition and Medicinal Chemistry

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Histone deacetylases (HDAC) are involved in several diseases including cancer, cardiovascular and neurodegenerative disorders, and the search for inhibitors is a current topic in drug discovery. Four HDAC inhibitors have already been approved by the FDA for cancer therapy and others are under clinical studies. However, the clinical utility of some of them is limited because of unfavorable toxicities associated with their broad range of HDAC inhibitory effects. Toxicity could be decreased by using HDAC inhibitors with improved specificity. To date, the most popular screening assays are based on fluorescence-labeled substrates incubated with an enzymatic source (cells extracts or recombinant isoforms). Here, we describe a high-throughput cell-based UHPLC-ESI-MS/MS assay able to rapidly predict activity against HDAC1 and HDAC6 in a cell environment. This method is predicted to be a useful tool to accelerate the search for class-selective HDAC inhibitors in drug discovery.

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Inhibition of histone deacetylase 4 increases cytotoxicity of docetaxel in gastric cancer cells

Abstract: These data support in vivo studies investigating the potential clinical use of HDAC4 inhibitors in combination with docetaxel for the treatment of gastric cancer, lowering treatment doses of docetaxel to reduce the burden of adverse side effects on patients.

Cited by 23 publications

References 36 publications

<p>Long Noncoding RNA <em>RGMB-AS1</em> Acts as a microRNA-574 Sponge Thereby Enhancing the Aggressiveness of Gastric Cancer via HDAC4 Upregulation</p>

<p>Long Noncoding RNA <em>RGMB-AS1</em> Acts as a microRNA-574 Sponge Thereby Enhancing the Aggressiveness of Gastric Cancer via HDAC4 Upregulation</p>

HDACs and HDAC Inhibitors in Cancer Development and Therapy

Cell-based multi-substrate assay coupled to UHPLC-ESI-MS/MS for a quick identification of class-specific HDAC inhibitors

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