scholarly journals The Histone Deacetylase Inhibitor BML-210 Influences Gene and Protein Expression in Human Promyelocytic Leukemia NB4 Cells via Epigenetic Reprogramming

2015 ◽  
Vol 16 (8) ◽  
pp. 18252-18269 ◽  
Author(s):  
Veronika Borutinskaitė ◽  
Rūta Navakauskienė
Keyword(s):  
Protein Expression ◽  
Histone Deacetylase ◽  
Histone Deacetylase Inhibitor ◽  
Promyelocytic Leukemia ◽  
Epigenetic Reprogramming ◽  
Nb4 Cells ◽  
Deacetylase Inhibitor ◽  
Gene And Protein Expression

26 HISTONE DEACETYLASE INHIBITOR SCRIPTAID IMPROVES EPIGENETIC REPROGRAMMING AND CLONING EFFICIENCY IN THE PIG

2015 ◽  
Vol 27 (1) ◽  
pp. 105
Author(s):  
S. Liang ◽  
T. Kim ◽  
N.-H. Kim ◽  
X.-S. Cui
Keyword(s):  
Histone Deacetylase ◽  
Histone Deacetylase Inhibitor ◽  
Histone H3 ◽  
Development Program ◽  
Donor Cell ◽  
Epigenetic Reprogramming ◽  
Republic Of Korea ◽  
Cloning Efficiency ◽  
Cell Stage ◽  
Deacetylase Inhibitor

After somatic cell nuclear transfer (SCNT), the epigenetic state of a differentiated donor cell nucleus must be reversed to the embryonic state. Incomplete epigenetic reprogramming and abnormal gene activation of the donor cell nuclei is thought to be the cause of low cloning efficiency. To improve cloning efficiency, we investigated the effect of scriptaid, a novel histone deacetylase inhibitor, on the in vitro development of porcine SCNT embryos were investigated. Cumulus cells collected from cumulus-oocyte complexes (COC) after 44 h of maturation were used for donor cell, and embryos were cultured in porcine zygote medium (PZM)-5 medium for 7 days. We found that treating SCNT embryos with 300 or 500 nM scriptaid for 20 h after activation increased developmental rate to the blastocyst stage (300 nM, 26.2%; 500 nM, 24.6% v. 100 nM, 18.3%; Ctrl, 15.7%; P < 0.05) and total cell numbers (300 nM, 43.5; 500 nM, 40.8 v. 100 nM, 33.8; Ctrl, 32.3; P < 0.05). Additionally, results of the TUNEL assay indicated that scriptaid decreased apoptosis (300 nM, 6.8% v. Ctrl, 11.4%; P < 0.05) in SCNT blastocysts. After the 300 nM scriptaid treatment, the levels of acetylated histone H3 lysine 9 and 5-hydroxymethylcytosines were increased (P < 0.05), and histone H3 lysine 9 trimethylation and 5-methylcytosine were decreased at the 1-cell stage, which might explain the enhanced (P < 0.05) transcript levels of mir-152, Oct4, Cdx2, and Bcl-xL and reduced (P < 0.05) transcription of Dnmt1, Casp3, and Bax in blastocysts. In conclusion, scriptaid enhances the developmental capacity by preventing apoptosis, and improves nuclear reprogramming in porcine SCNT embryos.This work was supported by the Bio-industry Technology Development Program, Ministry of Agriculture, Food and Rural Affairs, Republic of Korea, and by a grant from the Next-Generation BioGreen 21 Program (No. PJ009601 and PJ009098), Rural Development Administration, Republic of Korea.

scholarly journals Up-regulation of MDR1 and induction of doxorubicin resistance by histone deacetylase inhibitor depsipeptide (FK228) and ATRA in acute promyelocytic leukemia cells

Blood ◽  
2006 ◽  
Vol 107 (4) ◽  
pp. 1546-1554 ◽  
Author(s):  
Yoko Tabe ◽  
Marina Konopleva ◽  
Rooha Contractor ◽  
Mark Munsell ◽  
Wendy D. Schober ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Histone Deacetylase ◽  
Acute Promyelocytic Leukemia ◽  
Histone Deacetylase Inhibitor ◽  
Sequential Therapy ◽  
Promyelocytic Leukemia ◽  
Cross Resistance ◽  
Transcription Activator ◽  
Mrna Induction ◽  
Deacetylase Inhibitor

The multidrug resistance 1 (MDR1) gene product P-glycoprotein (P-gp) is frequently implicated in cross-resistance of tumors to chemotherapeutic drugs. In contrast, acute promyelocytic leukemia (APL) cells do not express MDR1 and are highly sensitive to anthracyclines. The combination of ATRA and the novel histone deacetylase inhibitor (HDACI) depsipeptide (FK228) induced P-gp expression and prevented growth inhibition and apoptosis in NB4 APL cells subsequently exposed to doxorubicin (DOX). ATRA/FK228 treatment after exposure to DOX, however, enhanced apoptosis. Both agents, ATRA or FK228, induced MDR1 mRNA. This effect was significantly enhanced by ATRA/FK228 administered in combination, due in part to increased H4 and H3-Lys9 acetylation of the MDR1 promoter and recruitment of the nuclear transcription factor Y alpha (NFYA) transcription activator to the CCAAT box. Cotreatment with specific P-gp inhibitor PSC833 reversed cytoprotective effects of ATRA/FK228. G1 cell-cycle arrest and p21 mRNA induction were also observed in response to ATRA/FK228, which may restrict DOX-induced apoptosis of cells in G2 phase. These results indicate that epigenetic mechanisms involving NF-YA transcription factor recruitment and histone acetylation are activated by ATRA and HDACI, induce MDR1 in APL cells, and point to the critical importance of mechanism-based sequential therapy in future clinical trials that combine HDAC inhibitors, ATRA, and anthracyclines.

scholarly journals Nanomicelles potentiate histone deacetylase inhibitor efficacy in vitro.

2020 ◽  
Author(s):  
Simone Pisano ◽  
Xiong Wang ◽  
Jezabel Garcia Parra ◽  
Andrea Gazze ◽  
Kadie Edwards ◽  
...  
Keyword(s):  
Histone Deacetylase ◽  
Cancer Progression ◽  
Histone Deacetylase Inhibitor ◽  
Time Window ◽  
Drug Carriers ◽  
Pluronic F127 ◽  
P53 Expression ◽  
Deacetylase Inhibitor ◽  
Gene And Protein Expression

Abstract Background. Amphiphilic block copolymers used as nanomicelle drug carriers can effectively overcome poor drug solubility and specificity issues. Hence, these platforms have a broad applicability in cancer treatment. In this study, Pluronic F127 was used to fabricate nanomicelles containing the histone deacetylase inhibitor SAHA, which has an epigenetic-driven anti-cancer effect in several tumor types. SAHA loaded nanomicelles were prepared using a thin-film drying method and characterized for size, surface charge, drug content and drug release properties. Loaded particles were tested for in vitro activity and their effect on cell-cycle and markers of cancer progression. Results. Following detailed particle characterization, cell proliferation experiments demonstrated that SAHA loaded nanomicelles more effectively inhibited the growth of HeLa and MCF-7 cell lines compared with free drug formulations. The 30nm SAHA containing nanoparticles were able to release up to 100% of the encapsulated drug over a 72h time window. Moreover, gene and protein expression analyses suggested that their cytoreductive effect was achieved through the regulation of p21 and p53 expression. SAHA was also shown to upregulate E-cadherin expression, potentially influencing tumor migration. Conclusions. This study highlights the opportunity to exploit pluronic-based nanomicelles for the delivery of compounds that regulate epigenetic processes, thus inhibiting cancer development and progression.

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