Trichostatin A - like Hydroxamate Histone Deacetylase Inhibitors as Therapeutic Agents: Toxicological Point of View

2004 ◽  
Vol 11 (12) ◽  
pp. 1629-1643 ◽  
Author(s):  
Tamara Vanhaecke ◽  
Peggy Papeleu ◽  
Greetje Elaut ◽  
Vera Rogiers
Keyword(s):  
Histone Deacetylase ◽  
Histone Deacetylase Inhibitors ◽  
Trichostatin A ◽  
Therapeutic Agents ◽  
Point Of View

scholarly journals Histone Deacetylase Inhibitors Increase the Embryogenic Potential and Alter the Expression of Embryogenesis-Related and HDAC-Encoding Genes in Grapevine (Vitis vinifera L., cv. Mencía)

Plants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1164
Author(s):  
Óscar Martínez ◽  
Verónica Arjones ◽  
María Victoria González ◽  
Manuel Rey
Keyword(s):  
Vitis Vinifera ◽  
Histone Deacetylase ◽  
Sodium Butyrate ◽  
Somatic Embryos ◽  
Histone Deacetylase Inhibitors ◽  
Trichostatin A ◽  
Vitis Vinifera L ◽  
Molecular Response ◽  
Embryogenic Competence ◽  
Encoding Genes

The low induction rates of somatic embryogenesis are one of the main limitations in its routine application in the grapevine (Vitis vinifera L.). The use of an induction medium containing histone deacetylase inhibitors (trichostatin A and, mainly, sodium butyrate) resulted in an improvement of the embryogenic responses in grapevine (cv. Mencía) cotyledonary and recently germinated somatic embryos. The relative expression of several grapevine genes related to embryogenic competence or encoding histone deacetylase enzymes was studied in cotyledonary somatic embryos that were cultured in the presence of 0.5 mM sodium butyrate. The results showed a significant overexpression of the BBM and VvSERK2 genes after 24 h of culture, whereas the VvWOX2 gene was underexpressed less in treated versus untreated explants. The results suggest that the inhibitor may trigger a molecular response related to an increase in embryogenic competence and changes in the expression of associated genes. The treatment with sodium butyrate also produced significant variations in the expression of several histone deacetylase enzyme-encoding genes. These results may enhance the possibility of obtaining somatic embryos, reducing the seasonal constraints associated with the use of floral explants in grapevines.

scholarly journals Comparison of Different Histone Deacetylase Inhibitors in Attenuating Inflammatory Pain in Rats

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Yu Mao ◽  
Jing Zhou ◽  
Xuesheng Liu ◽  
Erwei Gu ◽  
Zhi Zhang ◽  
...  
Keyword(s):  
Histone Deacetylase ◽  
Inflammatory Pain ◽  
Histone Deacetylase Inhibitors ◽  
Trichostatin A ◽  
Thermal Hyperalgesia ◽  
Pain Medicine ◽  
Once Daily ◽  
Analgesic Effects ◽  
Phenylbutyric Acid ◽  
Selection Of

Histone deacetylase inhibitors (HDACIs), which interfere with the epigenetic process of histone acetylation, have shown analgesic effects in animal models of persistent pain. The HDAC family comprises 18 genes; however, the different effects of distinct classes of HDACIs on pain relief remain unclear. The aim of this study was to determine the efficacy of these HDACIs on attenuating thermal hyperalgesia in persistent inflammatory pain. Persistent inflammatory pain was induced by injecting Complete Freund’s Adjuvant (CFA) into the left hind paw of rats. Then, HDACIs targeting class I (entinostat (MS-275)) and class IIa (sodium butyrate, valproic acid (VPA), and 4-phenylbutyric acid (4-PBA)), or class II (suberoylanilide hydoxamic acid (SAHA), trichostatin A (TSA), and dacinostat (LAQ824)) were administered intraperitoneally once daily for 3 or 4 days. We found that the injection of SAHA once a day for 3 days significantly attenuated CFA-induced thermal hyperalgesia from day 4 and lasted 7 days. In comparison with SAHA, suppression of hyperalgesia by 4-PBA peaked on day 2, whereas that by MS-275 occurred on days 5 and 6. Fatigue was a serious side effect seen with MS-275. These findings will be beneficial for optimizing the selection of specific HDACIs in medical fields such as pain medicine and neuropsychiatry.

scholarly journals Histone Deacetylase Inhibitors Down-Regulate bcl-2 Expression and Induce Apoptosis in t(14;18) Lymphomas

2005 ◽  
Vol 25 (5) ◽  
pp. 1608-1619 ◽  
Author(s):  
Hong Duan ◽  
Caroline A. Heckman ◽  
Linda M. Boxer
Keyword(s):  
Cell Cycle ◽  
Histone Deacetylase ◽  
Chromatin Immunoprecipitation ◽  
Histone Deacetylase Inhibitors ◽  
Antitumor Agents ◽  
Trichostatin A ◽  
Hdac Inhibitors ◽  
Transcriptional Level ◽  
Cycle Arrest ◽  
Induced Apoptosis

ABSTRACT Histone deacetylase (HDAC) inhibitors are promising antitumor agents, but they have not been extensively explored in B-cell lymphomas. Many of these lymphomas have the t(14;18) translocation, which results in increased bcl-2 expression and resistance to apoptosis. In this study, we examined the effects of two structurally different HDAC inhibitors, trichostatin A (TSA) and sodium butyrate (NaB), on the cell cycle, apoptosis, and bcl-2 expression in t(14;18) lymphoma cells. We found that in addition to potent cell cycle arrest, TSA and NaB also dramatically induced apoptosis and down-regulated bcl-2 expression, and overexpression of bcl-2 inhibited TSA-induced apoptosis. The repression of bcl-2 by TSA occurred at the transcriptional level. Western blot analysis and quantitative chromatin immunoprecipitation (ChIP) assay showed that even though HDAC inhibitors increased overall acetylation of histones, localized histone H3 deacetylation occurred at both bcl-2 promoters. TSA treatment increased the acetylation of the transcription factors Sp1 and C/EBPα and decreased their binding as well as the binding of CBP and HDAC2 to the bcl-2 promoters. Mutation of Sp1 and C/EBPα binding sites reduced the TSA-induced repression of bcl-2 promoter activity. This study provides a mechanistic rationale for the use of HDAC inhibitors in the treatment of human t(14;18) lymphomas.

Up-regulation of costimulatory/adhesion molecules by histone deacetylase inhibitors in acute myeloid leukemia cells

Blood ◽  
2000 ◽  
Vol 96 (12) ◽  
pp. 3847-3856 ◽  
Author(s):  
Takahiro Maeda ◽  
Masayuki Towatari ◽  
Hiroshi Kosugi ◽  
Hidehiko Saito
Keyword(s):  
Acute Myeloid Leukemia ◽  
Adhesion Molecules ◽  
Histone Deacetylase ◽  
Cell Lines ◽  
Myeloid Leukemia ◽  
Histone Deacetylase Inhibitors ◽  
Trichostatin A ◽  
Hl60 Cells ◽  
Hla Dr ◽  
Acute Myeloid

Abstract Histone deacetylase inhibitors (HDACIs) have been used to focus on the effects of inducing gene expression through the acetylation of histones which results in chromatin remodeling. The study explored whether HDACIs could induce the expression of costimulatory/adhesion molecules on acute myeloid leukemia (AML) cells, thereby effectively inducing tumor immunity. The expression of CD80, CD86, human leukocyte antigen (HLA)-DR, HLA-ABC, and intracellular adhesion molecule–1 (ICAM-1) was tested in human AML cell lines after the addition of HDACI, sodium butyrate (SB). Generally, increased expression of CD86 was observed by SB treatment in a majority of cell lines, and ICAM-1 was expressed in fewer cell lines. Essentially the same results were obtained using other HDACIs such as FR901228, trichostatin A, and trapoxin A. Quantitation of transcripts of CD86 accompanied with RNA synthesis inhibition assay and nuclear run-on assay revealed that SB up-regulates the CD86 expression transcriptionally. Furthermore, chromatin immunoprecipitation experiments showed that HDACI treatment caused remarkable acetylation on histone H3 and H4 at CD86 promoter chromatin in vivo. In 30 clinical AML samples, CD86 expression was significantly increased (P < .001) by SB treatment, and the expression of HLA-DR and ICAM-1 was moderately increased (P < .05) by SB treatment. Finally, the allogeneic mixed leukocyte reaction (allo-MLR) against HL60 cells pretreated with SB was enhanced 4-fold compared with allo-MLR obtained with non-treated HL60 cells. These results suggest that the immunotherapeutic use of HDACIs may become a novel tool for treatment of AML.

scholarly journals Effects of histone deacetylase inhibitors on estradiol-induced proliferation and hyperplasia formation in the mouse uterus

2005 ◽  
Vol 185 (3) ◽  
pp. 539-549 ◽  
Author(s):  
Andrei G Gunin ◽  
Irina N Kapitova ◽  
Nina V Suslonova
Keyword(s):  
Estrogen Receptor ◽  
Histone Acetylation ◽  
Histone Deacetylase ◽  
Sodium Butyrate ◽  
Histone Deacetylase Inhibitors ◽  
Trichostatin A ◽  
Progesterone Receptors ◽  
Estrogen Receptor Α ◽  
Mouse Uterus ◽  
Myometrial Cells

It is suggested that estrogen hormones recruit mechanisms controlling histone acetylation to bring about their effects in the uterus. However, it is not known how the level of histone acetylation affects estrogen-dependent processes in the uterus, especially proliferation and morphogenetic changes. Therefore, this study examined the effects of histone deacetylase blockers, trichostatin A and sodium butyrate, on proliferative and morphogenetic reactions in the uterus under long-term estrogen treatment. Ovari-ectomized mice were treated with estradiol dipropionate (4 μg per 100 g; s.c., once a week) or vehicle and trichostatin A (0.008 mg per 100 g; s.c., once a day) or sodium butyrate (1% in drinking water), or with no additional treatments for a month. In animals treated with estradiol and trichostatin A or sodium butyrate, uterine mass was increased, and abnormal uterine glands and atypical endometrial hyperplasia were found more often. Both histone deacetylase inhibitors produced an increase in the numbers of mitotic and bromodeoxyuridine-labelled cells in luminal and glandular epithelia, in stromal and myometrial cells. Levels of estrogen receptor-α and progesterone receptors in uterine epithelia, stromal and myometrial cells were decreased in mice treated with estradiol and trichostatin A or sodium butyrate. Expression of β-catenin in luminal and glandular epithelia was attenuated in mice treated with estradiol with trichostatin A or sodium butyrate. Both histone deacetylase inhibitors have similar unilateral effects; however the action of trichostatin A was more expressed than that of sodium butyrate. Thus, histone deacetylase inhibitors exert proliferative and morphogenetic effects of estradiol. The effects of trichostatin A and sodium butyrate are associated with changes in expression of estrogen receptor-α, progesterone receptors and β-catenin in the uterus.

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