Search results for "histone deacetylase inhibitor"
showing 10 items of 75 documents
Cytotoxic activity of the histone deacetylase 3-Selective inhibitor Pojamide on MDA-MB-231 triple-negative breast cancer cells
2019
We examined the effects of the ferrocene-based histone deacetylase-3 inhibitor Pojamide (N1-(2-aminophenyl)-N8-ferrocenyloctanediamide) and its two derivatives N1-(2-aminophenyl)-N6-ferrocenyladipamide and N1-(2-aminophenyl)-N8-ferroceniumoctanediamide tetrafluoroborate on triple-negative MDA-MB-231 breast cancer cells. Viability/growth assays indicated that only the first two compounds at 70 &mu
Biological Effect of a Hybrid Anticancer Agent Based on Kinase and Histone Deacetylase Inhibitors on Triple-Negative (MDA-MB231) Breast Cancer Cells
2016
We examined the effects of the histone deacetylase inhibitor (HDACi) suberoylanilide\ud hydroxamic acid (SAHA) combined with the vascular endothelial growth factor receptor-1/2 inhibitor\ud (3Z)-5-hydroxy-3-(1H-pyrrol-2-ylmethylidene)-2,3-dihydro-1H-indol-2-one on MDA-MB-231 breast\ud cancer cells (triple-negative) in the form of both a cocktail of the separate compounds and a chemically\ud synthesized hybrid (N-hydroxy-N'-[(3Z)-2-oxo-3-(1H-pyrrol-2-ylmethylidene)-2,3-dihydro-1H-indol-\ud 5-yl]octanediamide). Comparative flow cytometric and Western blot analyses were performed on\ud cocktail- and hybrid-treated cells to evaluate cell cycle distribution, autophagy/apoptosis modulation,\ud an…
The histone deacetylase inhibitor SAHA induces HSP60 nitration and its extracellular release by exosomal vesicles in human lung-derived carcinoma cel…
2015
// Claudia Campanella 1, 2, * , Antonella D'Anneo 3, * , Antonella Marino Gammazza 1, 2, * , Celeste Caruso Bavisotto 1, 2 , Rosario Barone 1, 2 , Sonia Emanuele 4 , Filippa Lo Cascio 1 , Emanuele Mocciaro 1 , Stefano Fais 5 , Everly Conway De Macario 6 , Alberto J.L. Macario 2, 6 , Francesco Cappello 1, 2 , Marianna Lauricella 4 1 Department of Experimental Biomedicine and Clinical Neurosciences, Section of Human Anatomy “Emerico Luna”, University of Palermo, Palermo, Italy 2 Euro-Mediterranean Institute of Science and Technology, Palermo, Italy 3 Department of Biological, Chemical and Pharmaceutical Sciences and Technologies, Laboratory of Biochemistry, University of Palermo, Palermo, Ita…
Molecular Signatures Associated with Treatment of Triple-Negative MDA-MB231 Breast Cancer Cells with Histone Deacetylase Inhibitors JAHA and SAHA
2017
Jay Amin Hydroxamic Acid (JAHA; N8-ferrocenylN1-hydroxy-octanediamide) is a ferrocene-containing analogue of the histone deacetylase inhibitor (HDACi) suberoylanilide hydroxamic acid (SAHA). JAHA’s cytotoxic activity on MDA-MB231 triple negative breast cancer (TNBC) cells at 72 h has been previously demonstrated with an IC50 of 8.45 M. JAHA’s lethal effect was found linked to perturbations of cell cycle, mitochondrial activity, signal transduction and autophagy mechanisms. In order to glean novel insights on how MDA-MB231 breast cancer cells respond to the cytotoxic effect induced by JAHA, and to compare the biological effect with the related compound SAHA, we have employed a combination of…
Inhibition of cell migration and induction of apoptosis by a novel class II histone deacetylase inhibitor, MCC2344.
2020
Epigenetic modifiers provide a new target for the development of anti-cancer drugs. The eraser histone deacetylase 6 (HDAC6) is a class IIb histone deacetylase that targets various non-histone proteins such as transcription factors, nuclear receptors, cytoskeletal proteins, DNA repair proteins, and molecular chaperones. Therefore, it became an attractive target for cancer treatment. In this study, virtual screening was applied to the MicroCombiChem database with 1162 drug-like compounds to identify new HDAC6 inhibitors. Five compounds were tested in silico and in vitro as HDAC6 inhibitors. Both analyses revealed 1-cyclohexene-1-carboxamide, 2-hydroxy-4,4-dimethyl-N-1-naphthalenyl-6-oxo- (MC…
Histone deacetylase inhibition by suberoylanilide hydroxamic acid: a therapeutic approach to treat human uterine leiomyoma.
2022
Objective To evaluate the effect of inhibition of histone deacetylases (HDACs) by suberoylanilide hydroxamic acid (SAHA) treatment of human uterine leiomyoma primary (HULP) cells in vitro on cell proliferation, cell cycle, extracellular matrix (ECM) formation, and transforming growth factor β3 (TGF-β3) signaling. Design Prospective study comparing uterine leiomyoma (UL) vs. adjacent myometrium (MM) tissue and cells with or without SAHA treatment. Setting Hospital and university laboratories. Patient(s) Women with UL without any hormone treatment. Intervention(s) Myomectomy or hysterectomy surgery in women for leiomyoma disease. Main Outcome Measure(s) HDAC activity was assessed by enzyme-li…
A Phase I Study of Intravenous LBH589, a Novel Cinnamic Hydroxamic Acid Analogue Histone Deacetylase Inhibitor, in Patients with Refractory Hematolog…
2006
Abstract Purpose: LBH589 is a novel histone deacetylase inhibitor that inhibits proliferation and induces apoptosis in tumor cell lines. In this phase I study, LBH589 was administered i.v. as a 30-minute infusion on days 1 to 7 of a 21-day cycle. Experimental Design: Fifteen patients (median age, 63 years; range, 42-87 years) with acute myeloid leukemia (13 patients), acute lymphocytic leukemia (1 patient), or myelodysplastic syndrome (1 patient) were treated with LBH589 at the following dose levels (mg/m2): 4.8 (3 patients), 7.2 (3 patients), 9.0 (1 patient), 11.5 (3 patient), and 14.0 (5 patients). The levels of histone acetylation were measured using quantitative flow cytometry and plasm…
Histone acetylation deficits in lymphoblastoid cell lines from patients with Rubinstein-Taybi syndrome.
2012
Background: Rubinstein-Taybi syndrome (RSTS) is a congenital neurodevelopmental disorder defined by postnatal growth deficiency, characteristic skeletal abnormalities and mental retardation and caused by mutations in the genes encoding for the transcriptional co-activators with intrinsic lysine acetyltransferase (KAT) activity CBP and p300. Previous studies have shown that neuronal histone acetylation is reduced in mouse models of RSTS. Methods: The authors identified different mutations at the CREBBP locus and generated lymphoblastoid cell lines derived from nine patients with RSTS carrying distinct CREBBP mutations that illustrate different grades of the clinical severity in the spectrum …
Belinostat in Patients With Relapsed or Refractory Peripheral T-Cell Lymphoma: Results of the Pivotal Phase II BELIEF (CLN-19) Study
2015
Purpose Peripheral T-cell lymphomas (PTCLs) represent a diverse group of non-Hodgkin lymphomas with a poor prognosis and no accepted standard of care for patients with relapsed or refractory disease. This study evaluated the efficacy and tolerability of belinostat, a novel histone deacetylase inhibitor, as a single agent in relapsed or refractory PTCL. Patients and Methods Patients with confirmed PTCL who experienced progression after ≥ one prior therapy received belinostat 1,000 mg/m2 as daily 30-minute infusions on days 1 to 5 every 21 days. Central assessment of response used International Working Group criteria. Primary end point was overall response rate. Secondary end points included …
Inhibition of Histone Deacetylase Activity in Human Endometrial Stromal Cells Promotes Extracellular Matrix Remodelling and Limits Embryo Invasion
2011
Invasion of the trophoblast into the maternal decidua is regulated by both the trophoectoderm and the endometrial stroma, and entails the action of tissue remodeling enzymes. Trophoblast invasion requires the action of metalloproteinases (MMPs) to degrade extracellular matrix (ECM) proteins and in turn, decidual cells express tissue inhibitors of MMPs (TIMPs). The balance between these promoting and restraining factors is a key event for the successful outcome of pregnancy. Gene expression is post-transcriptionally regulated by histone deacetylases (HDACs) that unpacks condensed chromatin activating gene expression. In this study we analyze the effect of histone acetylation on the expressio…