Category

Archives

NF-κB

BX-795 inhibits HSV-1 and HSV-2 replication by blocking the JNK/p38 pathways without interfering with PDK1 activity in host cells

16 | Nov 14 2019

Su AR et al. identified the anti-HSV activity of BX-795 and its targeting of the JNK/p38 MAP kinase pathways in host cells. [Read the Full Post]

RBBP8/CtIP suppresses P21 expression by interacting with CtBP and BRCA1 in gastric cancer

32 | Oct 24 2019

Yu Y et al. revealed the chromatin modification role of RBBP8, which could suppress the histone acetylation level of P21 promoter by recruiting CtBP co-repressor complex to BRCA1 binding site. [Read the Full Post]

Trichostatin A and 5-Aza-2'-Deoxycytidine influence the expression of cold-induced genes in Arabidopsis

37 | Oct 22 2019

Song Y et al. showed this result will advance our understanding of plant freezing responses and may provide a helpful strategy for cold tolerance improvement in crops. [Read the Full Post]

Panobinostat for the Treatment of Multiple Myeloma

86 | Oct 11 2019

Laubach JP et al. indicated The review focuses on panobinostat and its mechanism of action, pharmacokinetics, and clinical data in the treatment of relapsed or relapsed and refractory multiple myeloma. [Read the Full Post]

FK228 augmented temozolomide sensitivity in human glioma cells by blocking PI3K/AKT/mTOR signal pathways

91 | Oct 05 2019

Wu Y et al. suggested that FK228 augmented temozolomide sensitivity in human glioma cells partially by blocking PI3K/AKT/mTOR signal pathways. It thus may provide a promising target for improving the therapeutic outcome of TMZ-resistant gliomas, although further studies will be needed. [Read the Full Post]

Entinostat for the treatment of breast cancer

81 | Sep 20 2019

Trapani D et a. offered the rationale for combining HDAC inhibitors with immunotherapy, including therapeutic cancer vaccines. [Read the Full Post]

Acetazolamide potentiates the anti-tumor potential of HDACi, MS-275, in neuroblastoma

71 | Sep 20 2019

Bayat Mokhtari R et al. indicated the significant reduction in initial tumorigenicity and subsequent abrogation upon serial xenografting suggests potential elimination of the NB CSC fraction. The significant potentiation of MS-275 by AZ is a promising therapeutic approach and one amenable for administration to patients given their current clinical utility. [Read the Full Post]

LBH589 Inhibits Glioblastoma Growth and Angiogenesis Through Suppression of HIF-1α Expression

95 | Sep 14 2019

Yao ZG et al. supports the role of HDAC inhibitors as a therapeutic strategy to target tumor angiogenesis. [Read the Full Post]

Kinetic Tuning of HDAC Inhibitors Affords Potent Inducers of Progranulin Expression

107 | Sep 09 2019

Moreno-Yruela C et al. demonstrated induction of PGRN expression by fast-on/fast-off, highly potent, macrocyclic HDAC inhibitors with ethyl ketone or ethyl ester Zn2+ binding groups. [Read the Full Post]

SOX7 regulates MAPK/ERK-BIM mediated apoptosis in cancer cells

98 | Sep 09 2019

Sun QY et al. revealed an unappreciated role of SOX7 in regulation of cellular apoptosis through control of MAPK/ERK-BIM signaling. [Read the Full Post]

Quantifying Risk Pathway Crosstalk Mediated by miRNA to Screen Precision drugs for Breast Cancer Patients

110 | Sep 03 2019

Xu Y et al. offers an effective way to screen precision drugs for various breast cancer subtype treatments. We also dissected the mechanism of optimal therapeutic drugs, which may provide novel insight into the precise treatment of cancer and promote researches on the mechanisms of action of drugs. [Read the Full Post]

Vorinostat-eluting poly(DL-lactide-co-glycolide) nanofiber-coated stent for inhibition of cholangiocarcinoma cells

113 | Sep 02 2019

Kwak TW et al. suggested the vorinostat nanofiber-coated stent may be a promising candidate for CCA treatment. [Read the Full Post]

Oncogenic enhancer of zeste homolog 2 is an actionable target in patients with non-small cell lung cancer

105 | Sep 02 2019

Shi B et al. showed that overexpression of EZH2 is a negative prognostic indicator. Increased EZH2 expression predicts for response to HDAC inhibitors and thus could serve as a biomarker for selecting NSCLC patients for treatment with HDAC inhibitors. [Read the Full Post]

Metformin and 4SC-202 synergistically promote intrinsic cell apoptosis by accelerating ΔNp63 ubiquitination and degradation in oral squamous cell carcinoma

172 | Aug 25 2019

He Y et al. revealed that ΔNp63 mediated anticancer effects of metformin and 4SC-202, as overexpression or suppression of ΔNp63 could attenuate or facilitate the apoptosis rate of OSCC under metformin or/and 4SC-202 treatment. Collectively, metformin and 4SC-202 synergistically promote intrinsic apoptosis through accelerating ubiquitin-mediated degradation of ΔNp63 in OSCC, and this co-treatment can serve as a potential therapeutic scheme for OSCC. [Read the Full Post]

Kinetic Tuning of HDAC Inhibitors Affords Potent Inducers of Progranulin Expression

0 | Jul 27 2019

Moreno-Yruela C et al. demonstrated induction of PGRN expression by fast-on/fast-off, highly potent, macrocyclic HDAC inhibitors with ethyl ketone or ethyl ester Zn2+ binding groups. [Read the Full Post]

Genomic testing, tumor microenvironment and targeted therapy of Hedgehog-related human cancers

86 | Jul 03 2019

Katoh M indicated that SMO inhibitors can remodel the immunosuppressive TME that is dominated by M2-like tumor-associated macrophages (M2-TAMs), myeloid-derived suppressor cells and regulatory T cells, and thus, a Phase I/II clinical trial of the immune checkpoint inhibitor pembrolizumab with or without vismodegib in BCC patients is ongoing. [Read the Full Post]

Curaxin CBL0137 has the potential to reverse HIV-1 latency

86 | Jun 24 2019

Jean MJ et al. indicated that CBL0137 possesses capabilities as a LRA and could be considered for the "shock and kill" approach. [Read the Full Post]

Age-related macular degeneration (AMD) mitochondria modulate epigenetic mechanisms in retinal pigment epithelial cells

108 | Jun 23 2019

Nashine S et al. revealed that AMD mitochondria regulate epigenetic mechanisms i.e., methylation and acetylation status. Demethylation using 5-Aza-2'-deoxycytidine (DAC) caused differential expression of VEGF-A gene in AMD cells. Trichostatin A (TSA), an HDAC inhibitor, also influenced protein levels of VEGF-A, HIF1α, NFκB, and CFH in AMD cells. This study might advance the field of AMD research since in addition to highlighting the critical role of nuclear-mitochondrial interactions that influence epigenetic mechanisms in AMD patients, this work suggests epigenetic profiles as potential therapeutic targets for AMD. [Read the Full Post]

BAY 87-2243 sensitizes hepatocellular carcinoma Hep3B cells to histone deacetylase inhibitors treatment via GSK-3β activation

96 | Jun 22 2019

Li YL et al. found that BAY 87-2243 combined with HDAC inhibitors might be an attractive chemotherapy strategy for HCC therapy. [Read the Full Post]

Reciprocal Relationship Between HDAC2 and P-Glycoprotein/MRP-1 and Their Role in Steroid Resistance in Childhood Nephrotic Syndrome

98 | Jun 22 2019

Singh H et al. found that reduced HDAC2 and increased P-gp/MRP-1 activity may play a role in response to steroids in childhood NS. HDAC2 and P-gp/MRP-1 are in reciprocal relationship with each other. [Read the Full Post]

Histone deacetylase 6 inhibitor ACY-1215 protects against experimental acute liver failure by regulating the TLR4-MAPK/NF-κB pathway

293 | Jun 19 2019

Zhang WB et al. showed that ACY-1215 has potential therapeutic value in mice with ALF by directly inhibiting inflammatory response via regulation of the TLR4-MAPK/NF-kB pathway. [Read the Full Post]

The 3-Phosphoinositide-Dependent Protein Kinase 1 Inhibits Rod Photoreceptor Development

105 | Jun 04 2019

Xing T et al. indicated that PDPK-1 and other intrinsic kinases downstream of IGF-1 are key regulators of rod photoreceptor formation. [Read the Full Post]

ITF2357 transactivates Id3 and regulate TGFβ/BMP7 signaling pathways to attenuate corneal fibrosis

525 | Apr 21 2019

Lim RR et al. concludd that ITF2357 is a potential anti-fibrotic drug that exerts its action via activation of Id3, a downstream target of TGFβ/BMP7 signaling pathways. [Read the Full Post]

The histone deacetylase inhibitor givinostat (ITF2357) exhibits potent anti-tumor activity against CRLF2-rearranged BCP-ALL

219 | Apr 13 2019

Savino AM et al. indicated givinostat killed ruxolitinib-resistant cells and potentiated the effect of current chemotherapy. Thus, givinostat in combination with conventional chemotherapy may represent an effective therapeutic option for these difficult-to-treat subsets of ALL. Lastly, the selective killing of cancer cells by givinostat may allow the design of reduced intensity regimens in CRLF2-rearranged Down syndrome-associated BCP-ALL patients with an overall benefit in terms of both toxicity and related complications. [Read the Full Post]

Targeting HDAC3 Activity with RGFP966 Protects Against Retinal Ganglion Cell Nuclear Atrophy and Apoptosis After Optic Nerve Injury

216 | Mar 12 2019

Schmitt HM et al. showed the inhibition of HDAC3 activity with systemic dosing of RGFP966 prevents apoptosis-related histone deacetylation and attenuates RGC loss after acute optic nerve injury. [Read the Full Post]

The expression of endothelin-1 in chronic lymphocytic leukemia is controlled by epigenetic mechanisms and extracellular stimuli

109 | Jan 31 2019

Martinelli S et al. demonstrated the fundamental role of NF-kB signalling pathway in promoting and maintaining ET-1 expression in CLL cells, both in basal conditions and after CD40 activation. [Read the Full Post]

Inhibition of Histone Deacetylases Permits Lipopolysaccharide-Mediated Secretion of Bioactive IL-1β via a Caspase-1-Independent Mechanism

749 | Jan 11 2019

Stammler D et al. indicated that in addition to the conventional inflammasome-dependent IL-1β cleavage pathway, dendritic cells and macrophages are capable of generating, secreting, and processing bioactive IL-1β by a novel, caspase-8-dependent mechanism. [Read the Full Post]

Inhibition of Histone Deacetylase 3 (HDAC3) Mediates Ischemic Preconditioning and Protects Cortical Neurons against Ischemia in Rats

310 | Jan 09 2019

Yang X et al. demonstrated that the inhibition of HDAC3 preconditions the brain against ischemic insults, indicating a new approach to evoke endogenous protection against stroke. [Read the Full Post]

Differential effects of histone deacetylase inhibitors on cellular drug transporters and their implications for using epigenetic modifiers in combination chemotherapy

0 | Jan 07 2019

Valdez BC et al. further imply the possibility of antagonistic effects when HDAC inhibitors are combined with anthracyclines and other MDR1 drug ligands in chemotherapy. [Read the Full Post]

Enhanced efficacy of 5-fluorouracil in combination with a dual histone deacetylase and phosphatidylinositide 3-kinase inhibitor (CUDC-907) in colorectal cancer cells

424 | Dec 26 2018

Hamam R et al. revealed, for the first time, the enhanced inhibitory effect of CUDC-907 against CRC cells when combined with 5-FU, supporting the application of this combination as a potential therapeutic strategy in CRC treatment. [Read the Full Post]

CUDC-907 Promotes Bone Marrow Adipocytic Differentiation Through Inhibition of Histone Deacetylase and Regulation of Cell Cycle

458 | Dec 26 2018

Ali D et al. revealed that HDAC, PI3K, and cell cycle genes are important regulators of BMA formation and demonstrate that adipocyte differentiation of hBMSCs is associated with complex changes in a number of epigenetic and genetic pathways, which can be targeted to regulate BMA formation. [Read the Full Post]

Differential effects of histone deacetylase inhibitors on cellular drug transporters and their implications for using epigenetic modifiers in combination chemotherapy

334 | Dec 20 2018

Valdez BC et al. further implied the possibility of antagonistic effects when HDAC inhibitors are combined with anthracyclines and other MDR1 drug ligands in chemotherapy. [Read the Full Post]

Parthenolide inhibits the initiation of experimental autoimmune neuritis

545 | Dec 09 2018

Zhang M et al. indicated that PAR plays dual roles in EAN and it is not proper to be applied in autoimmune diseases of nervous system. [Read the Full Post]

Suppression of αvβ6 Integrin Expression by Polymicrobial Oral Biofilms in Gingival Epithelial Cells

404 | Dec 05 2018

Bi J et al. indicated that including lipopeptides, may downregulate αvβ6 integrin expression in the pocket epithelium and thus promote epithelial cell-driven pro-inflammatory response in periodontal disease. [Read the Full Post]

Effects of the histone deacetylase inhibitor 'Scriptaid' on the developmental competence of mouse embryos generated through round spermatid injection

426 | Nov 11 2018

Kong P et al. supported through grants from the National Key Research Program of China (No. 2016YFC1304800); the National Natural Science Foundation of China (Nos: 81170756, 81571486); the Natural Science Foundation of Shanghai (Nos: 15140901700, 15ZR1424900) and the Programme for Professor of Special Appointment (Eastern Scholar) at Shanghai Institutions of Higher Learning. There are no conflicts of interest to declare. [Read the Full Post]

Curcumin and its cyclohexanone analogue inhibited human Equilibrative nucleoside transporter 1 (ENT1) in pancreatic cancer cells

658 | Nov 08 2018

Revalde JL et al. concluded that curcumin and A13 are inhibitors of the ENT1 transporter, but only at high concentrations (2-20µM). [Read the Full Post]

Synergistic anti-cancer effects of epigenetic drugs on medulloblastoma cells

367 | Nov 03 2018

Yuan J et al. suggested that the application of HDACi in combination with drugs that target DNMT may represent a promising option for the treatment of medulloblastoma. [Read the Full Post]

Romidepsin induces G2/M phase arrest via Erk/cdc25C/cdc2/cyclinB pathway and apoptosis induction through JNK/c-Jun/caspase3 pathway in hepatocellular carcinoma cells

400 | Oct 13 2018

Sun WJ et al. offered proof-of-concept for use of Romidepsin as a novel class of chemotherapy in the treatment of HCC. [Read the Full Post]

Characterization of cholesterol homeostasis in sphingosine-1-phosphate lyase-deficient fibroblasts reveals a Niemann-Pick disease type C-like phenotype with enhanced lysosomal Ca2+ storage

0 | Aug 08 2018

Vienken H et al. showed that both a primary defect in cholesterol trafficking and S1P lyase deficiency cause overlapping phenotypic alterations, and challenge the present view on the role of sphingosine in lysosomal Ca2+ homeostasis. [Read the Full Post]

Histone Deacetylase Inhibitor RGFP109 Overcomes Temozolomide Resistance by Blocking NF-κB-Dependent Transcription in Glioblastoma Cell Lines

0 | Aug 08 2018

Li ZY et al. showed that RGFP109, an HDAC inhibitor, in combination with TMZ may be a therapeutic candidate for patients with temozolomide-resistant GBM. [Read the Full Post]

The role of Runx2 in facilitating autophagy in metastatic breast cancer cells

674 | Aug 05 2018

Tandon M et al. revealed a novel regulatory mechanism of autophagy via Runx2 and provide molecular insights into the role of autophagy in metastatic cancer cells. [Read the Full Post]

AR-42 induces apoptosis in human hepatocellular carcinoma cells via HDAC5 inhibition

890 | Aug 02 2018

Zhang M et al. demonstrated for the first time that AR-42 targets HDAC5 and induces apoptosis in human hepatocellular carcinoma cells. AR-42 therefore shows potential as a new drug candidate for HCC therapy. [Read the Full Post]

HDAC6 promotes cell proliferation and confers resistance to temozolomide in glioblastoma

635 | Aug 01 2018

Wang Z et al. suggested that the inhibition of HDAC6 may be a promising strategy for the treatment of glioblastoma. [Read the Full Post]

HDAC6 inhibition prevents TNF-α-induced caspase 3 activation in lung endothelial cell and maintains cell-cell junctions

1841 | Jul 31 2018

Yu J et al. suggested that HDAC6 inhibition is a potent therapeutic strategy against inflammatory injury to endothelial cells. [Read the Full Post]

The histone deacetylase inhibitor valproic acid inhibits NKG2D expression in natural killer cells through suppression of STAT3 and HDAC3

612 | Jul 31 2018

Ni L et al. showed that VPA is a potent inhibitor of STAT3 phosphorylation and demonstrate that histone acetylation and STAT3 tyrosine705 phosphorylation cooperate in regulating NKG2D expression in NK cells. [Read the Full Post]

The HDAC inhibitor SB939 overcomes resistance to BCR-ABL kinase Inhibitors conferred by the BIM deletion polymorphism in chronic myeloid leukemia

629 | Jul 22 2018

Rauzan M et al. demonstrated that SB939 overcomes BIM deletion polymorphism-induced TKI resistance, and suggest that SB939 may be useful in treating CML patients with BIM deletion-associated TKI resistance. [Read the Full Post]

Therapeutic fetal-globin inducers reduce transcriptional repression in hemoglobinopathy erythroid progenitors through distinct mechanisms

576 | Jul 22 2018

Dai Y et al. identified clinical-stage oral therapeutics which inhibit or displace major co-repressors of γ-globin gene transcription and may suggest a rationale for combination therapy to produce enhanced efficacy. [Read the Full Post]

Identification of cytotoxic agents disrupting synovial sarcoma oncoprotein interactions by proximity ligation assay

0 | Jul 20 2018

Laporte AN, et al. indicated this assay can be applied in a high-throughput format for drug discovery in fusion-oncoprotein associated cancers where key effector partners are known. [Read the Full Post]

Millepachine, a potential topoisomerase II inhibitor induces apoptosis via activation of NF-κB pathway in ovarian cancer

966 | Jul 19 2018

Wu W et al. identified that MIL exhibited anti-tumor activity through inhibiting topoisomerase II activity to induce tumor cells DNA damage, and MIL-activated NF-κB pathway showed a pro-apoptotic function in response to DNA damage. [Read the Full Post]

EGCG inhibited bladder cancer SW780 cell proliferation and migration both in vitro and in vivo via down-regulation of NF-κB and MMP-9

913 | Jul 18 2018

Luo KW et al. demonstrated that EGCG was effective in inhibition SW780 cell proliferation and migration, and presented first evidence that EGCG inhibited SW780 tumor growth by down-regulation of NF-κB and MMP-9. [Read the Full Post]

Loss of α-Tubulin Acetylation Is Associated with TGF-β-induced Epithelial-Mesenchymal Transition

2038 | Jul 03 2018

Gu S et al. demonstrated that acetylated α-tubulin can serve as a marker of EMT and that HDAC6 represents an important regulator during EMT process. [Read the Full Post]

PTEN activation through K163 acetylation by inhibiting HDAC6 contributes to tumour inhibition

0 | Jul 03 2018

Meng Z, et al. indicated that PTEN activation by inhibiting HDAC6 significantly contributed to tumour inhibition. Therefore, non-selective HDAC or HDAC6-specific inhibitors may be more clinically suitable to treat tumours without PTEN mutations or deletions. [Read the Full Post]

Therapeutic effects of histone deacetylase inhibitors in a murine asthma model

591 | Jun 28 2018

Ren Y, et al. suggested that treatment with HDAC inhibitors can reduce airway inflammation, airway remodeling, and airway hyperresponsiveness in chronic allergic airway disease in mice. [Read the Full Post]

LTR12 promoter activation in a broad range of human tumor cells by HDAC inhibition

617 | Jun 28 2018

Krönung SK et al. showed that inhibition of HDAC1-3 is sufficient for LTR12 activation. Importantly, HDAC inhibitors induce LTR12 activity not only in testicular cancer cells, but also in cells derived from many additional tumor species. Finally, we characterize the transcription factor NF-Y as a mediator of LTR12 promoter activity and HDAC inhibitor-induced apoptosis, in the context of widespread genomic binding of NF-Y to specific LTR12 sequences. Thus, HDAC inhibitor-driven LTR12 activation represents a generally applicable means to induce proapoptotic genes in human cancer cells. [Read the Full Post]

HDAC5, a potential therapeutic target and prognostic biomarker, promotes proliferation, invasion and migration in human breast cancer

680 | Jun 27 2018

Li A et al. indicated that HDAC5 is a promising prognostic marker and drug target for BC and that the combination of LMK-235 and bortezomib presents a novel therapeutic strategy for BC. [Read the Full Post]

HPOB, an HDAC6 inhibitor, attenuates corticosterone-induced injury in rat adrenal pheochromocytoma PC12 cells by inhibiting mitochondrial GR translocation and the intrinsic apoptosis pathway

578 | Jun 26 2018

Li ZY et al. suggested that the anti-apoptotic activity of HDAC6 inhibition against the mitochondria-mediated impairment pathway might be mechanistically linked to the hyperacetylation of Hsps and consequent suppression of GR translocation to the mitochondria. [Read the Full Post]

Acetylation of p53 Protein at Lysine 120 Up-regulates Apaf-1 Protein-and-Sensitizes-the-Mitochondrial-Apoptotic-Pathway

771 | Jun 23 2018

Yun T et al. found that histone deacetylase (HDAC) inhibitors, including butyrate, augment Lys-120 acetylation of p53 and thus Apaf-1 expression by inhibiting HDAC1. [Read the Full Post]

Identification of cytotoxic agents disrupting synovial sarcoma oncoprotein interactions by proximity ligation assay

0 | Jun 21 2018

Laporte AN et al. reported use of the proximity ligation assay to confirm the oncogenic association of SS18-SSX with its co-factor TLE1 in multiple human synovial sarcoma cell lines and in surgically-excised human tumor tissue. SS18-SSX/TLE1 interactions are disrupted by class I HDAC inhibitors and novel small molecule inhibitors. This assay can be applied in a high-throughput format for drug discovery in fusion-oncoprotein associated cancers where key effector partners are known. [Read the Full Post]

HDAC6-mediated EGFR stabilization and activation restrict cell response to sorafenib in non-small cell lung cancer cells

691 | Jun 15 2018

Wang Z et al. explained the failure of Phase III trial of sorafenib in improving overall survival of advanced NSCLC patients and bear possible implications for the improvement on the efficacy of sorafenib in treatment of NSCLC. [Read the Full Post]

Encapsulation of curcumin in polyelectrolyte nanocapsules and their neuroprotective activity

1132 | Jun 10 2018

Szczepanowicz K et al. indicated the utility of PLL/PGA shell nanocapsules as a promising, alternative way of curcumin delivery for neuroprotective purposes with improved efficiency and reduced toxicity. [Read the Full Post]

Targeting HSF1 disrupts HSP90 chaperone function in chronic lymphocytic leukemia

505 | Jun 01 2018

Ganguly S et al. provided a strong rationale to target HSF1 and test the activity of minnelide against human CLL. [Read the Full Post]

Acetylation of p53 Protein at Lysine 120 Up-regulates Apaf-1 Protein and Sensitizes the Mitochondrial Apoptotic Pathway

0 | May 12 2018

Yun T et al. found that HDAC inhibitors can induce p53 acetylation at lysine 120, which in turn enhances mitochondrion-mediated apoptosis through transcriptional up-regulation of Apaf-1. [Read the Full Post]

Reduced expression of CD109 in tumor-associated endothelial cells promotes tumor progression by paracrine interleukin-8 in hepatocellular carcinoma

379 | May 04 2018

Ye BG et al. indicated that CD109 expression on tumor vessels is a potential prognostic marker for HCC, and its reduced expression on TEC promoted tumor progression by paracrine IL-8. [Read the Full Post]

HCV core protein binds to gC1qR to induce A20 expression and inhibit cytokine production through MAPKs and NF-κB signaling pathways

1011 | May 04 2018

Song X et al. suggested that HCV core protein ligates gC1qR to induce A20 expression in macrophages via P38, JNK and NF-κB signaling pathways, which leads to a low-grade chronic inflammation during HCV infection. It represents a novel mechanism by which HCV usurps the host for persistence. [Read the Full Post]

TGF-β1 activates the canonical NF-κB signaling to promote cell survival and proliferation in dystrophic muscle fibroblasts in vitro.

0 | Apr 21 2018

Ma ZY et al. suggested that TGF-β1 prevents apoptosis and cell cycle arrest in dystrophic muscle fibroblasts through the canonical NF-κB signaling pathway. [Read the Full Post]

Evodiamine inhibits PDGF‑BB‑induced proliferation of rat vascular smooth muscle cells through the suppression of cell cycle progression and oxidative stress

1093 | Apr 13 2018

Ge X et al. provided important insights into the mechanisms underlying the vasoprotective actions of evodiamine and suggested that it may be a useful therapeutic agent for the treatment of vascular occlusive disease. [Read the Full Post]

cAMP signaling increases histone deacetylase 8 expression via the Epac2-Rap1A-Akt pathway in H1299 lung cancer cells

636 | Mar 14 2018

Park JY et al. indicated the Epac-Rap1-Akt pathway mediates cAMP signaling-induced inhibition of JNK-dependent HDAC8 degradation, and the resulting HDAC8 increase augments cisplatin-induced apoptosis by repressing TIPRL expression in H1299 lung cancer cells. [Read the Full Post]

Osteoclast-Primed Foxp3+ CD8 T Cells Induce T-bet, Eomesodermin, and IFN-γ To Regulate Bone Resorption.

0 | Mar 11 2018

Shashkova EV et al. demonstrated a novel link between NF-κB signaling and induction of IFN-γ in TcREG and establish an important role for IFN-γ in TcREG-mediated protection from bone loss. [Read the Full Post]

Panobinostat induces apoptosis via production of reactive oxygen species and synergizes with topoisomerase inhibitors in cervical cancer cells

0 | Mar 10 2018

Wasim L et al. suggest a combination therapy using inhibitors of histone deacetylase and topoisomerase together could hold the promise for an effective targeted therapeutic strategy. [Read the Full Post]

Valproic acid potentiates the anticancer activity of capecitabine in vitro and in vivo in breast cancer models via induction of thymidine phosphorylase expression

1079 | Mar 10 2018

Terranova-Barberio M et al. suggested that the combination of HDACi (e.g., VPA) and capecitabine is an innovative antitumor strategy that warrants further clinical evaluation for the treatment of metastatic breast cancer. [Read the Full Post]

Insulin-induced cytokine production in macrophages causes insulin resistance in hepatocytes

489 | Mar 05 2018

Manowsky J et al. indicated that hyperinsulinemia per se might contribute to the low-grade inflammation prevailing in overweight and obese patients and thereby promote the development of insulin resistance particularly in the liver, because the insulin concentration in the portal circulation is much higher than in all other tissues. [Read the Full Post]

Advanced glycation end products regulate anabolic and catabolic activities via NLRP3-inflammasome activation in human nucleus pulposus cells

729 | Mar 05 2018

Song Y et al. revealed that accumulation of AGEs in NP tissue may initiate inflammation-related degeneration of the intervertebral disc via activation of the NLRP3 inflammasome. [Read the Full Post]

Overexpression of GAB2 in ovarian cancer cells promotes tumor growth and angiogenesis by upregulating chemokine expression

0 | Mar 04 2018

Duckworth C et al. suggested that overexpression of GAB2 in ovarian cancer cells promotes tumor growth and angiogenesis by upregulating expression of CXCL1, CXCL2 and CXCL8 that is IKKβ-dependent. Co-targeting IKKβ and PI3K pathways downstream of GAB2 might be a promising therapeutic strategy for ovarian cancer that overexpresses GAB2. [Read the Full Post]

Chromatin Architecture Emerges during Zygotic Genome Activation Independent of Transcription

494 | Feb 24 2018

Hug CB et al. offered insight into when spatial organization of the genome emerges and identify a key factor that helps trigger this architecture. [Read the Full Post]

A novel, rapid method to compare the therapeutic windows of oral anticoagulants using the Hill coefficient

1234 | Feb 17 2018

Zhang Q et al. showed a significant variation among the Hill coefficients, suggesting a similar variation in therapeutic windows among anticoagulants in our assay. [Read the Full Post]

TGF-β1 activates the canonical NF-κB signaling to promote cell survival and proliferation in dystrophic muscle fibroblasts in vitro

0 | Feb 09 2018

Ma ZY et al. suggested that TGF-β1 prevents apoptosis and cell cycle arrest in dystrophic muscle fibroblasts through the canonical NF-κB signaling pathway. [Read the Full Post]

TGF-β1 activates the canonical NF-κB signaling to promote cell survival and proliferation in dystrophic muscle fibroblasts in vitro

448 | Feb 08 2018

Ma ZY et al. suggested that TGF-β1 prevents apoptosis and cell cycle arrest in dystrophic muscle fibroblasts through the canonical NF-κB signaling pathway. [Read the Full Post]

Epigenetic Regulation of Interleukin 6 by Histone Acetylation in Macrophages and Its Role in Paraquat-Induced Pulmonary Fibrosis

1803 | Feb 06 2018

Hu L et al. indicated IL-6 functioning through EMT in PQ-induced pulmonary fibrosis was regulated dynamically by HDAC and HAT both in vitro and in vivo via epigenetically regulating chromatin accessibility. [Read the Full Post]

A novel HDAC6 inhibitor Tubastatin A: Controls HDAC6-p97/VCP-mediated ubiquitination-autophagy turnover and reverses Temozolomide-induced ER stress-tolerance in GBM cells

1307 | Jan 27 2018

Li ZY et al. showed that the balance of HDAC6-p97/VCP was crucial to ERST-associated TMZ resistance and that HDAC6 inhibition might be a synergistic target and strategy along with TMZ for the improvement of clinical glioma treatment. [Read the Full Post]

Diabetes mellitus stimulates pancreatic cancer growth and epithelial-mesenchymal transition-mediated metastasis via a p38 MAPK pathway

1056 | Jan 19 2018

Wang L et al. revealed that p38 MAPK inhibitors may provide a novel intervention strategy for diabetic pancreatic cancer treatment. [Read the Full Post]

Sensitization of melanoma cells to alkylating agent-induced DNA damage and cell death via orchestrating oxidative stress and IKKβ inhibition

478 | Jan 16 2018

Tse AK et al. illustrated a new direction in nitrosourea treatment, and revealed that the combination of ROS-inducing IKKβ inhibitors with nitrosoureas can be potentially exploited for melanoma therapy. [Read the Full Post]

Acetylation of p53 Protein at Lysine 120 Up-regulates Apaf-1 Protein and Sensitizes the Mitochondrial Apoptotic Pathway

0 | Jan 03 2018

Yun T et al. induced p53 acetylation at lysine 120, which in turn enhances mitochondrion-mediated apoptosis through transcriptional up-regulation of Apaf-1. [Read the Full Post]

Activation-of-Nur77-in-microglia-attenuates-proinflammatory-mediators-production-and-protects-dopaminergic-neurons-from-inflammation-induced-cell-death

583 | Jan 02 2018

Liu TY et al. revealed the first evidence that Nur77 was an important modulator in microglia function that associated with microglia-mediated dopaminergic neurotoxicity, and thus modulation of Nur77 may represent a potential novel target for treatment for neurodegenerative disease. [Read the Full Post]

Activation of oncogenic pathways in classical Hodgkin lymphoma by decitabine: A rationale for combination with small molecular weight inhibitors.

949 | Dec 29 2017

Swerev TM et al. concluded that targeting of oncogenic pathways of cHL may improve efficacy of DNA-demethylating therapy in cHL. [Read the Full Post]

Endosulfan induces cell dysfunction through cycle arrest resulting from DNA damage and DNA damage response signaling pathways

1038 | Dec 26 2017

Ni L et al. provided a new insight for mechanism of endosulfan-induced cardiovascular toxicity which will be helpful in future prevention of cardiovascular diseases induced by endosulfan. [Read the Full Post]

Combined use of irinotecan with histone deacetylase inhibitor belinostat could cause severe toxicity by inhibiting SN-38 glucuronidation via UGT1A1

1281 | Dec 23 2017

Wang L et al. found the potential clinical significance, as a large proportion of patients could be at risk of developing severe toxicity if irinotecan is co-administered with belinostat. [Read the Full Post]

Ubiquitination and regulation of AURKA identifies a hypoxia-independent E3 ligase activity of VHL

968 | Dec 19 2017

Hasanov E et al. identified VHL as an E3 ligase with important cellular functions under both normoxic and hypoxic conditions. [Read the Full Post]

Ultrasound Enhances the Expression of Brain-Derived Neurotrophic Factor in Astrocyte Through Activation of TrkB-Akt and Calcium-CaMK Signaling Pathways

0 | Sep 29 2017

Liu SH et al. found that LIPUS stimulation might play a crucial and beneficial role in neurodegenerative diseases. [Read the Full Post]

Preparation and Biochemical Analysis of Classical Histone Deacetylases

0 | Sep 28 2017

Mohseni J et al. established methods for assaying HDAC activities, as well as introduces more recently developed nontraditional assays. [Read the Full Post]

Preparation and Biochemical Analysis of Classical Histone Deacetylases

0 | Sep 28 2017

Villagra A et al. reviewed some of the older established methods for assaying HDAC activities, as well as introduces more recently developed nontraditional assays. [Read the Full Post]

Evaluation of the Therapeutic Potential of the Novel Isotype Specific HDAC Inhibitor 4SC-202 in Urothelial Carcinoma Cell Lines.

1221 | Sep 17 2017

Pinkerneil M et al. combined inhibition of HDAC1, HDAC2 and HDAC3 seems to be a promising treatment strategy for UC. [Read the Full Post]

Transcript, methylation and molecular docking analyses of the effects of HDAC inhibitors, SAHA and Dacinostat, on SMN2 expression in fibroblasts of SMA patients

0 | Sep 16 2017

Mohseni J et al. showed that SAHA and Dacinostat increased SMN2 transcript and protein levels and promoted demethylation of the SMN2 gene. [Read the Full Post]

HMGB1 exacerbates bronchiolitis obliterans syndrome via RAGE/NF-κB/HPSE signaling to enhance latent TGF-β release from ECM

0 | Sep 14 2017

He L et al. suggested that HMGB1 and HPSE could be viable targets for prevention and intervention of fibrotic diseases such BOS after lung transplantation. [Read the Full Post]

Atg7 Knockdown Augments Concanavalin A-Induced Acute Hepatitis through an ROS-Mediated p38/MAPK Pathway

784 | Sep 13 2017

Zhuang Y et al. revealed that autophagy may attenuate macrophage-mediated inflammatory response to ConA and may be the potential therapeutic targets for acute liver injury. [Read the Full Post]

Neuronal Soluble Fas Ligand Drives M1-Microglia Polarization after Cerebral Ischemia

0 | Sep 07 2017

Meng HL et al. involved the activation of JAK2/STAT3 and NF-κB signaling pathways. [Read the Full Post]

Neuronal Soluble Fas Ligand Drives M1-Microglia Polarization after Cerebral Ischemia

0 | Aug 30 2017

Meng HL et al. involved the activation of JAK2/STAT3 and NF-κB signaling pathways. [Read the Full Post]

Identification of cytotoxic agents disrupting synovial sarcoma oncoprotein interactions by proximity ligation assay

1380 | Aug 27 2017

Laporte AN et al. report use of the proximity ligation assay to confirm the oncogenic association of SS18-SSX with its co-factor TLE1 in multiple human synovial sarcoma cell lines and in surgically-excised human tumor tissue. SS18-SSX/TLE1 interactions are disrupted by class I HDAC inhibitors and novel small molecule inhibitors. This assay can be applied in a high-throughput format for drug discovery in fusion-oncoprotein associated cancers where key effector partners are known. [Read the Full Post]

Brain-Penetrating Histone Deacetylase Inhibitor RG2833 Reduces the Viability of Human Malignant Melanoma Cell Lines SK-MEL-5 and SK-MEL-28 in vitro

1362 | Aug 24 2017

Lauren Green found that concentrations of RG2833 that effectively inhibited HDAC activity also resulted in reduced melanoma cell growth and viability. These results demonstrate the effectiveness of RG2833 in reducing the growth and viability of malignant melanoma cells in vitro and warrant further investigation of the potential therapeutic use of RG2833 and related compounds in the battle against cancer. [Read the Full Post]

Sodium phenylbutyrate antagonizes prostate cancer through the induction of apoptosis and attenuation of cell viability and migration

1459 | Aug 23 2017

Xu Y et al. found that the viability of PCa cells was significantly inhibited by SPB treatment. As illustrated by flow cytometry, for DU145 cell line the average apoptotic rate of SPB-treated cells was significantly lower than that of the control group (P<0.05); similar results were also seen for PC3 (P<0.05). SPB administration also attenuated the colony formation and migration abilities in both cell lines. The expression level of survivin in SPB-treated cells was significantly downregulated, while the phosphorylation of p-38 and ERK was enhanced. Furthermore, in vivo tumor formation of both cell lines was suppressed by SPB as well. [Read the Full Post]

Acetylation of p53 Protein at Lysine 120 Up-regulates Apaf-1 Protein and Sensitizes the Mitochondrial Apoptotic Pathway

1586 | Aug 23 2017

Yun T et al. found that histone deacetylase (HDAC) inhibitors, including butyrate, augment Lys-120 acetylation of p53 and thus Apaf-1 expression by inhibiting HDAC1. In p53-null cells, transfection of wild-type but not K120R mutant p53 can restore the p53-dependent sensitivity to butyrate. Strikingly, transfection of acetylation-mimicking K120Q mutant p53 is sufficient to up-regulates Apaf-1 in a manner independent of butyrate treatment. Therefore, HDAC inhibitors can induce p53 acetylation at lysine 120, which in turn enhances mitochondrion-mediated apoptosis through transcriptional up-regulation of Apaf-1. [Read the Full Post]

Panobinostat induces apoptosis via production of reactive oxygen species and synergizes with topoisomerase inhibitors in cervical cancer cells

1564 | Jul 20 2017

Wasim L et al. suggested a combination therapy using inhibitors of histone deacetylase and topoisomerase together could hold the promise for an effective targeted therapeutic strategy. [Read the Full Post]

Histone deacetylase inhibitor panobinostat induces calcineurin degradation in multiple myeloma

1713 | Jul 19 2017

Imai Y et al. findings underscore the usefulness of calcineurin-targeted therapy in MM patients, including patients who are resistant to bortezomib. [Read the Full Post]

IFN-α potentiates the direct and immune-mediated antitumor effects of epigenetic drugs on both metastatic and stem cells of colorectal cancer

0 | Jul 07 2017

Buoncervello M et al. opened a new frontier on the suitability of IFN-α in association with epigenetics as a novel and promising therapeutic approach for CRC management. [Read the Full Post]

The histone deacetylase inhibiting drug Entinostat induces lipid accumulation in differentiated HepaRG cells.

1711 | Jun 26 2017

Nunn AD et al. demonstrated the power of Entinostat to promote lipid synthesis and storage, allowing reduced systemic sugar levels and sequestration of toxic metabolites within protected protein-coated droplets, suggesting a potential therapeutic strategy for diseases such as diabetes and metabolic syndrome. [Read the Full Post]

PRRT2 inhibits the proliferation of glioma cells by modulating unfolded protein response pathway

1626 | Jun 12 2017

Bi G et al. found that PRRT2 as a tumor suppressor in glioma and provide a promising target for potential therapeutic intervention. [Read the Full Post]

Mechanical stimulation orchestrates the osteogenic differentiation of human bone marrow stromal cells by regulating HDAC1

0 | Jun 01 2017

Wang J et al. found that mechanical stimulation orchestrates genes expression involved in the osteogenic differentiation of BMSCs via the direct regulation of HDAC1, and the therapeutic inhibition of HDAC1 may be an efficient strategy for enhancing bone formation under mechanical stimulation. [Read the Full Post]

Porphyromonas gingivalis induces IL-8 and IFN-gamma secretion and apoptosis in human extravillous trophoblast derived HTR8/SVneo cells via activation of ERK1/2 and p38 signaling pathways

828 | May 27 2017

Ren H et al. demonstrated for the first time that activation of ERK1/2 and p38 MAPK pathways participates in P. gingivalis-induced inflammation and apoptosis. [Read the Full Post]

Myofibril growth during cardiac hypertrophy is regulated through dual phosphorylation and acetylation of the actin capping protein CapZ

0 | May 23 2017

Lin YH et al. showed that PE treatment of NRVMs results in decreased binding of HDAC3 to myofibrils, suggesting a signal-dependent mechanism for the regulation of sarcomere-associated CapZβ1 acetylation. [Read the Full Post]

Valproic Acid and Other HDAC Inhibitors Upregulate FGF21 Gene Expression and Promote Process Elongation in Glia by Inhibiting HDAC2 and 3.

0 | May 10 2017

Leng Y et al. provided a new mechanism via which histone deacetylase 2 and 3 participate in upregulating fibroblast growth factor 21 transcription and extending process outgrowth in glia. [Read the Full Post]

Valproic Acid and Other HDAC Inhibitors Upregulate FGF21 Gene Expression and Promote Process Elongation in Glia by Inhibiting HDAC2 and 3.

0 | May 09 2017

Leng Y et al. provided a new mechanism via which histone deacetylase 2 and 3 participate in upregulating fibroblast growth factor 21 transcription and extending process outgrowth in glia. [Read the Full Post]

Atorvastatin antagonizes the visfatin-induced expression of inflammatory mediators via the upregulation of NF-κB activation in HCAECs

865 | May 04 2017

Shi KL et al. provided a potential use for atorvastatin and visfatin in the pathogenesis of HCAEC dysfunction. [Read the Full Post]

The histone deacetylase inhibitor PCI-24781 as a putative radiosensitizer in pediatric glioblastoma cell lines

0 | May 01 2017

de Andrade PV et al demonstrate that HDACi PCI-24781 has a radiosensitizing profile that compromises the repair of double-strand DNA breaks in cells of pediatric GBM treated with radiotherapy. [Read the Full Post]

Atorvastatin antagonizes the visfatin-induced expression of inflammatory mediators via the upregulation of NF-κB activation in HCAECs

882 | Apr 26 2017

Shi KL et al. provided a potential use for atorvastatin and visfatin in the pathogenesis of HCAEC dysfunction. T [Read the Full Post]

Inhibition of Phospho-S6 Kinase, a Protein Involved in the Compensatory Adaptive Response, Increases the Efficacy of Paclitaxel in Reducing the Viability of Matrix-Attached Ovarian Cancer Cells.

2728 | Apr 17 2017

Choi JI et al found that addition of BX795 or CCT128930 to inhibit pS6 (S240/S244) or pS6 (S235/S236) restricted the compensatory adaptive response to paclitaxel in HeyA8 and SKOV3 cells. These inhibitors increased the efficacy of paclitaxel in reducing cancer cell viability. [Read the Full Post]

Signaling factors and pathways of α-particle irradiation induced bilateral bystander responses between Beas-2B and U937 cells

0 | Apr 12 2017

Fu J et al disclosed novel signaling cascades of macrophage-mediated bilateral bystander responses that the release of TNF-α and IL-8 regulated by MAPK and NF-κB pathways synergistically increased cellular injury after α-particle irradiation. [Read the Full Post]

Resveratrol delays polycystic kidney disease progression through attenuation of nuclear factor κB-induced inflammation

0 | Apr 09 2017

Wu M et al found that the NF-κB signaling pathway is activated and partly responsible for inflammation in polycystic kidney tissues. Targeting inflammation through resveratrol could be a new strategy for PKD treatment in the future. [Read the Full Post]

PTEN activation through K163 acetylation by inhibiting HDAC6 contributes to tumour inhibition

0 | Mar 23 2017

Meng Z et al indicated that PTEN activation by inhibiting HDAC6 significantly contributed to tumour inhibition. Therefore, non-selective HDAC or HDAC6-specific inhibitors may be more clinically suitable to treat tumours without PTEN mutations or deletions. [Read the Full Post]

Overexpression of GAB2 in ovarian cancer cells promotes tumor growth and angiogenesis by upregulating chemokine expression

1411 | Mar 22 2017

Duckworth C et al suggestec that overexpression of GAB2 in ovarian cancer cells promotes tumor growth and angiogenesis by upregulating expression of CXCL1, CXCL2 and CXCL8 that is IKKβ-dependent. Co-targeting IKKβ and PI3K pathways downstream of GAB2 might be a promising therapeutic strategy for ovarian cancer that overexpresses GAB2. [Read the Full Post]

HDAC4 mediates IFN-γ induced disruption of energy expenditure-related gene expression by repressing SIRT1 transcription in skeletal muscle cells

2726 | Mar 13 2017

Fang M et al revealed a role for HDAC4 in regulating cellular energy output and as such provide insights into rationalized design of novel anti-diabetic therapeutics. [Read the Full Post]

Epigenetically maintained SW13+ and SW13- subtypes have different oncogenic potential and convert with HDAC1 inhibition

0 | Feb 17 2017

When compared to the SW13- subtype, SW13+ cells have restored BRM expression, increased metastatic capacity, and significantly different expression of a variety of chromatin remodeling factors including those involved with histone acetylation and methylation. These data are consistent with a multistep mechanism of SW13- to SW13+ conversion and subtype stabilization: histone hypermodification results in the altered expression of chromatin remodeling factors and chromatin epigenetic enzymes and the re-expression of BRM which results in restoration of SWI/SNF complex function and leads to changes in chromatin structure and gene expression that stabilize the SW13+ phenotype. [Read the Full Post]

Lipopolysaccharide supports maintaining the stemness of CD133(+) hepatoma cells through activation of the NF-κB/HIF-1α pathway

1065 | Feb 10 2017

The study of Lai FB, et al. highlighted LPS as a potential target for developing new therapeutic approaches to eliminate CSCs during the treatment of HCC. [Read the Full Post]

PTEN activation through K163 acetylation by inhibiting HDAC6 contributes to tumour inhibition

2167 | Jan 27 2017

Meng Z et al. found that non-selective HDAC or HDAC6-specific inhibitors may be more clinically suitable to treat tumours without PTEN mutations or deletions. [Read the Full Post]

Overexpression of GAB2 in ovarian cancer cells promotes tumor growth and angiogenesis by upregulating chemokine expression

992 | Jan 25 2017

Duckworth C, et al.'s findings suggest that overexpression of GAB2 in ovarian cancer cells promotes tumor growth and angiogenesis by upregulating expression of CXCL1, CXCL2 and CXCL8 that is IKKβ-dependent. Co-targeting IKKβ and PI3K pathways downstream of GAB2 might be a promising therapeutic strategy for ovarian cancer that overexpresses GAB2. [Read the Full Post]

Osteoclast-Primed Foxp3+ CD8 T Cells Induce T-bet, Eomesodermin, and IFN-γ To Regulate Bone Resorption

1094 | Dec 27 2016

The results of Shashkova EV et al.'s study demonstrate a novel link between NF-κB signaling and induction of IFN-γ in TcREG and establish an important role for IFN-γ in TcREG-mediated protection from bone loss. [Read the Full Post]

The histone deacetylase inhibiting drug Entinostat induces lipid accumulation in differentiated HepaRG cells

1961 | Dec 27 2016

The results of Nunn AD, et al. demonstrated the power of Entinostat to promote lipid synthesis and storage, allowing reduced systemic sugar levels and sequestration of toxic metabolites within protected protein-coated droplets, suggesting a potential therapeutic strategy for diseases such as diabetes and metabolic syndrome. [Read the Full Post]

IFN-α potentiates the direct and immune-mediated antitumor effects of epigenetic drugs on both metastatic and stem cells of colorectal cancer

2301 | Dec 22 2016

The findings of Buoncervello M et al. open a new frontier on the suitability of IFN-α in association with epigenetics as a novel and promising therapeutic approach for CRC management. [Read the Full Post]

Neuronal Soluble Fas Ligand Drives M1-Microglia Polarization after Cerebral Ischemia

1130 | Dec 03 2016

Meng HL et al. 's study explored sFasL expression in neurons and the potential role of neuronal sFasL in modulating the microglial phenotypes. [Read the Full Post]

HMGB1 exacerbates bronchiolitis obliterans syndrome via RAGE/NF-kB/HPSE signaling to enhance latent TGF-b release from ECM

1162 | Dec 01 2016

He L et al.’s data suggest that HMGB1 and HPSE could be viable targets for prevention and intervention of fibrotic diseases such BOS after lung transplantation. [Read the Full Post]

Transcript, methylation and molecular docking analyses of the effects of HDAC inhibitors, SAHA and Dacinostat, on SMN2 expression in fibroblasts of SMA patients.

0 | Nov 29 2016

With the exception on the effect of Dacinostat in Type II cells, Mohseni J, et al have shown that SAHA and Dacinostat increased SMN2 transcript and protein levels and promoted demethylation of the SMN2 gene. [Read the Full Post]

Evaluation of the Therapeutic Potential of the Novel Isotype Specific HDAC Inhibitor 4SC-202 in Urothelial Carcinoma Cell Lines

2194 | Nov 28 2016

Specific pharmacological inhibition of class I HDACs by 4SC-202 impairs UC cell viability, inducing cell cycle disturbances and cell death. Combined inhibition of HDAC1, HDAC2 and HDAC3 seems to be a promising treatment strategy for UC. [Read the Full Post]

Transcript, methylation and molecular docking analyses of the effects of HDAC inhibitors, SAHA and Dacinostat, on SMN2 expression in fibroblasts of SMA patients

3160 | Nov 25 2016

With the exception on the effect of Dacinostat in Type II cells, Mohseni J et al showed that SAHA and Dacinostat increased SMN2 transcript and protein levels and promoted demethylation of the SMN2 gene. [Read the Full Post]

Preparation and Biochemical Analysis of Classical Histone Deacetylases

2308 | Nov 24 2016

Villagra A et al. reviewed some of the older established methods for assaying HDAC activities, as well as introduces more recently developed nontraditional assays. [Read the Full Post]

Epigenetically maintained SW13+ and SW13- subtypes have different oncogenic potential and convert with HDAC1 inhibition.

2209 | Nov 08 2016

Davis MR, et al. found that The efficacy of HDAC inhibitors in inducing subtype switching was determined by immunofluorescence and qPCR. [Read the Full Post]

Lipopolysaccharide supports maintaining the stemness of CD133(+) hepatoma cells through activation of the NF-κB/HIF-1α pathway

1287 | Nov 04 2016

Lai FB et al. highlighted LPS as a potential target for developing new therapeutic approaches to eliminate CSCs during the treatment of HCC. [Read the Full Post]

Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests

2264 | Oct 31 2016

Shinde V, et al. found that the concept based on the indices D p and D i offers the possibility to quantitatively express the propensity of test compounds to interfere with normal development. [Read the Full Post]

Mechanical stimulation orchestrates the osteogenic differentiation of human bone marrow stromal cells by regulating HDAC1

4482 | Oct 27 2016

Wang J et al. found that mechanical stimulation orchestrates genes expression involved in the osteogenic differentiation of BMSCs via the direct regulation of HDAC1, and the therapeutic inhibition of HDAC1 may be an efficient strategy for enhancing bone formation under mechanical stimulation. [Read the Full Post]

Myofibril growth during cardiac hypertrophy is regulated through dual phosphorylation and acetylation of the actin capping protein CapZ

2374 | Oct 20 2016

Lin YH et al. showed that PE treatment of NRVMs results in decreased binding of HDAC3 to myofibrils, suggesting a signal-dependent mechanism for the regulation of sarcomere-associated CapZβ1 acetylation. [Read the Full Post]

Valproic Acid and Other HDAC Inhibitors Upregulate FGF21 Gene Expression and Promote Process Elongation in Glia by Inhibiting HDAC2 and 3

2480 | Oct 09 2016

Leng Y et al. provided a new mechanism via which histone deacetylase 2 and 3 participate in upregulating fibroblast growth factor 21 transcription and extending process outgrowth in glia. [Read the Full Post]

The histone deacetylase inhibitor PCI-24781 as a putative radiosensitizer in pediatric glioblastoma cell lines

2209 | Sep 28 2016

De Andrade PV et al demonstrated that HDACi PCI-24781 has a radiosensitizing profile that compromises the repair of double-strand DNA breaks in cells of pediatric GBM treated with radiotherapy. [Read the Full Post]

Resveratrol delays polycystic kidney disease progression through attenuation of nuclear factor κB-induced inflammation

3584 | Sep 09 2016

Wu M et al. demonstrated that targeting inflammation through resveratrol could be a new strategy for PKD treatment in the future. [Read the Full Post]

The interferon-related developmental regulator 1 is a key factor for human papillomavirus-induced NFкB inhibition

4225 | Mar 24 2015

Tummers et al. found hrHPV impairs immune response by inhibiting the acetylation of NFкB/RelA K310 in keratinocytes. [Read the Full Post]

Bromodomain and extra-terminal proteins are required in STAT5-mediated transcription

4424 | Mar 23 2015

Pinz et al. found deacetylase inhibitors lead to the delocalization of the bromodomain and extra-terminal (BET) protein Brd2, as well as Brd2-related factor TBP to hyperacetylated chromatin, via the global upregulation of histone acetylation. [Read the Full Post]

CY190602, a novel DNA/HDAC dual-targeting drug with enhanced anti-cancer potency

8252 | Mar 19 2015

Liu et al. demonstrated a novel bendamustine-derived drug, CY190602, enhanced anticancer potency. [Read the Full Post]

Histone deacetylase inhibitors have negative effects on the elimination of HIV-infected cells by cytotoxic T-Lymphocytes

4312 | Mar 02 2015

Jones et al. tested the impact of three HDACis, suberanilohydroxamic acid (SAHA), romidepsin and panobinostat, in clinical development on immune effectors functions, such as T-cell effector. [Read the Full Post]

The combination of broadly neutralizing antibodies and viral inducers can suppress the establishment of HIV-1 latent reservoir

5365 | Feb 13 2015

Halper-Stromerg et al. demonstrated that broadly neutralizing antibodies (bNAbs) can suppress the establishment of a silent reservoir in humanized mice. [Read the Full Post]

The inhibition of class I histone deacetylases by butyrate can suppress acute gout arthritis

4169 | Jan 22 2015

Cleophas et al. found high concentration of short-chain fatty acid butyrate provides anti-inflammatory effect by inhibiting of histone deacetylases (HDACs) in acute gout arthritis. [Read the Full Post]

Butyrate acts as an suppressor against colonic tumor in gnotobiotic mouse models

4436 | Jan 19 2015

Donohoe et al. demonstrated dietary fiber suppress tumor progress in a microbiota- and butyrate-dependent manner. [Read the Full Post]

Snail also acts as a transactivator for the expression of tumor-associated cytokines

5704 | Jan 16 2015

Hsu et al. demonstrated the underlying mechanism of Snail-mediated target gene transactivation, and also identified several target genes. [Read the Full Post]

Inflammatory signaling plays a critical role in vertebrates embryonic hematopoiesis

1992 | Jan 09 2015

He et al. found inflammatory signaling is critical in zebrafish and mouse embryonic hematopoiesis without infection or pathological inflammation. [Read the Full Post]

Innate immunity-induced IRF3 signaling suppress TGF-β via Smad

4850 | Dec 23 2014

By investigating the innate host defense, Xu et al. found RIG-I-Like receptor (RLR) signaling suppress TGF-β via activation of Interferon regulatory factor 3 (IRF3). [Read the Full Post]

IncRNA BCAR4 regulates cancer development cooperated with chemokine signals

6049 | Dec 09 2014

Xing et al. demonstrated the mechanism of BCAR4, a disease-related Inc RNA, in regulation signaling pathways in breast cancer metastasis. [Read the Full Post]

The binding of mutant p53 and DAB2IP increase the invasion of inflammation induced cancer cells

4125 | Dec 08 2014

Minin et al. inflammatory cytokines can increase the invasive behavior of cancer cells with p53 missense mutants (mutp53). [Read the Full Post]

KIAA1199 provides a connection between oncogenic signaling of NF-κB and EGFR

5322 | Dec 01 2014

Shostak et al. showed the connection between the two oncogenic cascades by identifying a key factor, KIAA1199, that associated with human papillomavirus (HPV) infection. [Read the Full Post]

The effect of panobinostat on HIV latency disruption in a phase 1/2 clinical trial

4807 | Oct 22 2014

Rasmussen et al. found panobinostat, a histone deacetylase inhibitor, has the ability to activate infected cells from HIV latency. They also tested the safety of this strategy on phase 1/2 clinical trial. The effect of panobinostat treatment was not significant in reducing the number of latently infected cells. However, panobinostat effectively disrupt HIV latency in vivo. [Read the Full Post]

PCI34051 is a potent histone deacetylase 8 inhibitor

3754 | Mar 06 2014

PCI-34051 is a potent and specific HDAC8 inhibitor with IC50 of 10 nM. It has greater than 200-fold selectivity over HDAC1 and 6. [Read the Full Post]

PCI 24781 is a broad spectrum hydroxamic acid based inhibitor of HDAC

3650 | Feb 25 2014

HDAC activity is measured using a continuous trypsin-coupled assay. [Read the Full Post]

SB939 is a novel histone deacetylase inhibitor with improved

3797 | Feb 11 2014

SB939 has a 100-fold greater selectivity for HDACs than for Zn-binding non-HDAC enzymes, receptors, and ion channels. [Read the Full Post]

MS 275 is a benzamide histone deacetylase inhibitor undergoing clinical trials

3768 | Jan 22 2014

MS-275 shows inhibitory to HDACs by 2-amino group. MS-275 induces accumulation of p21WAF1/CIP1 and gelsolin in K562 cell. [Read the Full Post]

MS 275 is a benzamide histone deacetylase inhibitor

3675 | Jan 21 2014

MS-275 shows inhibitory to HDACs by 2'-amino group. MS-275 induces accumulation of p21WAF1/CIP1 and gelsolin in K562 cell. [Read the Full Post]

SB939 is a novel histone deacetylas inhibitor with improved

3684 | Dec 23 2013

SB939 is a potent pan-HDAC inhibitor with IC50 of 40-140 nM with exception for HDAC6. It has no activity against the class III isoenzyme SIRT I. [Read the Full Post]

Givinostat is a histone deacetylase inhibitor with potential

3354 | Dec 17 2013

Givinostat (ITF2357) is a potent HDAC inhibitor for HDAC2, HDAC1B and HDAC1A with IC50 of 10 nM, 7.5 nM and 16 nM. [Read the Full Post]

CUDC 101 is a potent inhibitor of histone deacetylase

3519 | Nov 25 2013

CUDC-101 is a potent multi-targeted inhibitor against HDAC, EGFR and HER2 with IC50 of 4.4 nM, 2.4 nM, and 15.7 nM, and inhibits class I/II HDACs, but not class III, Sir-type HDACs. [Read the Full Post]

SB939 is a pan histone deacetylase inhibitor binding

3573 | Nov 04 2013

SB939 has a 100-fold greater selectivity for HDACs than for Zn-binding non-HDAC enzymes, receptors, and ion channels. [Read the Full Post]

Trichostatin A is an organic compound that serves as an antifungal antibiotic

3385 | Oct 25 2013

Trichostatin A (TSA) is an HDAC inhibitor with IC50 of ~1.8 nM – HDAC8 is the only known member of the HDAC-family that is not affected by TSA. [Read the Full Post]

MS275 strongly inhibits HDAC1 and HDAC3 with IC50

3329 | Aug 29 2013

MS-275 exhibits great antitumor activity against human tumor xenografts except HCT-15 at 49 mg/kg. [Read the Full Post]

Tubastatin A was substantially more selective than the known HDAC6 inhibitor

3523 | Apr 28 2013

Tubastatin A is substantially selective for all 11 HDAC isoforms and maintains over 1000-fold selectivity against all isoforms excluding HDAC8, where it has approximately 57-fold selectivity. [Read the Full Post]

Vorinostat is a member of a larger class of compounds that inhibit histone deacetylases

3416 | Mar 06 2013

A total of 155 children were screened for enrollment in the study, with 110 children being excluded on the basis of the enrollment criteria. The predominant reasons for exclusion were based on either the age or the weight criterion. Forty-five Vorinostat children meeting enrollment criteria for the PK substudy were enrolled: 23 in the AL arm and 22 in the AQ-AS arm. [Read the Full Post]

HDAC is also shown to occur in an inhibitor

3767 | Oct 24 2012

These include KIT, RET, STK11 LKB1. These are all known cancer associated kinases that have dysregulated signaling in various human cancers, including GIST and hematological malignancies, papillary thyroid cancer and lung cancer [Read the Full Post]

VORINOSTAT: A HYDROXAMIC ACID

4244 | Sep 10 2012

VORINOSTAT OR SAHA (SUBEROYLANILIDE HYDROXAMIC ACID): Histone deacetylase inhibitors or HDACi perform functions in the regulation of gene expression, cell cycle arrest, apoptosis stimulation in cancer cells and variation of different pathways in cancer cells such as cellular proliferation due to hyperacetylating the histone proteins. HDAC inhibitors are one of the leading approach for the treatment of cancers and tumors and among these inhibitors Vorinostat SAHA is the important one. This inhibitor is found to have strong anti-oncogenic properties and the Vorinostat structure contains a molecules having hydroxamic acid. For both classes of HDAC inhibitors that is class I and II the Vorinostat IC50 is about 50nM. The solubility of Vorinostat is around 2mg/ml in ethanol where it is highly soluble in DMSO in which 65mg/ml is Vorinostat solubility but it is poorly soluble in water. Stability of Vorinostat is of about 24 months when stored at -20 ºC. One can purchase Vorinostat for research purpose from any of the Vorinostat supplier by spending Vorinostat price that is $26 for a vial of 100mg however the prices are variably depending upon purity of the salt and supplier. Amongst different HDAC inhibitors the first FDA approved such inhibitor is Vorinostat HDAC inhibitor for the treatment of T-cell lymphoma. [Read the Full Post]

HISTONE DEACETYLASE INHIBITORS BEYOND CANCER TREATMENT

3868 | Sep 02 2012

EPIGENEITIC MODULATION AND HDAC INHIBITORS In cellular genome a major part comprises of histone proteins and these proteins upon addition of acetyle group perform some of the most important cellular pathways are controlled by these proteins, these pathways include cell growth and proliferation and programmed cell death. When the acetyle group is detached from histones the process of apoptosis starts because most of the genetic expression of some vital proteins is ceased due to deacetylation and in addition to this the DNA condensation is also increased due to increased DNA binding capacity. It has been noticed that during neurodegenerative diseases the process of deacetylation is disturbed which leads to different types of cancers and tumors which is characterized by uncontrolled cell proliferation. These studies encouraged the discoveries of HDAC inhibitors and also enlighten the HDAC inhibition process. In preclinical and clinical evaluations HDAC inhibitions have been applied which leads to the successful and detailed use of this process by good number of researchers. Various activity assays are available for the estimation of HDACs levels. Kits are available for such assays however these can also be performed manually in the lab. HDAC inhibitors analysis can also be done by a nonisotopic assay which is microplate reader compatible and test for robotic screening and compound profiling is also available or another assay which is suitable for high throughput screening. [Read the Full Post]

HDAC INHIBITORS AGAINST TOMORS

4115 | Aug 22 2012

HDAC INHIBITION: A SOURCE OF EPIGENETIC MODULATION Histone acetylation is an essential process in functions like cell growth and cellular death by causing the inhibition of transcription of proteins caused by removal of the acetyl groups from the histone proteins, as a result of which the binding of DNA is increased, causing it to be condensed. A disturbance in this phenomenon leads to an uncontrolled growth of the cells that leads to the production of tumors and neurodegenerative diseases as well. HDAC inhibition is performed to treat various forms of tumors by using HDAC-2 inhibitors. Different successful studies at various levels have elucidated the mechanism of action of HDAC inhibitors leading to their enormous applications in various preclinical and clinical trials. The levels of HDAC inhibitors can be assessed by the use of different sort of assays specially developed for this reason. These chemical assays can be performed in laboratory by using various kits. The researchers can perform nonisotopic HDAC inhibitor and microplate reader compatible assay and the one for the robotic screening and compound profiling. In addition to it a simple flourogenic assay can also be used for the high-throughput screening process. [Read the Full Post]

HDAC INHIBITORS AGAINST CANCERS

3928 | Aug 15 2012

HDAC INHIBITION AND EPIGENETIC MODULATION An important process; histone acetylation is related to cellular functions for example cell death and cell growth stimulating the protein transcription inhibition by removing the acetyl groups from the related proteins hence causing the increase in DNA binding and making it more condensed. Any disturbance in this process leads to the uncontrolled cellular growth that further leads to the tumor production and also the neurodegenerative diseases. Histone deacetylase inhibition is carried out for the treatment of different types of tumors by using the HDAC-6 inhibitors. Various successful studies at different levels have exhibited the mode of action of histone deacetylase inhibitors further leading to their vast area of applications in different clinical and pre-clinical studies. The HDAC inhibitors levels can be analyzed by using various types of assays specifically developed for this purpose. These assays can be carried out in the labs through different kits. Researchers can perform microplate reader compatible assay and the nonisotopic HDAC inhibitor assay and also the one for compound profiling and robotic screening. In addition to this simple flourogenic assay may also be carried out for the process of high-throughput screening. [Read the Full Post]

HDAC INHIBITORS AGAINST CANCERS

3723 | Aug 01 2012

EPIGENETIC MODULATION VIA HDAC INHIBITION: Histones acetylation is vital process in the functions like cellular growth and cell death by inhibiting the transcription of proteins which is caused by the removal of acetyl groups from histones as a result the DNA binding increases and DNA is condensed. When this process is disturbed it leads to uncontrolled growth of cells leading to the formation of cancers and also neurodegenerative diseases. HDAC inhibition for the treatment of cancer comes by the use of HDAC inhibitors. Successful studies elucidating mechanisms of HDAC inhibitors led to their vast applications in different clinical and preclinical studies. HDAC levels can be assessed by using various assays developed for this purpose. These assays can be performed in lab by the help of kits. Researchers can perform microplate reader compatible and nonisotopic HDAC inhibitor assay and one for compound profiling and robotic screening and in addition to this simply a flourogenic assay can be performed for high-throughput screening. [Read the Full Post]

INHIBITORS OF HISTONE DEACETYLASE

3046 | Jul 13 2012

HDAC INHIBITORS AND EPIGENEITIC VARIATION Different functions of the cell like apoptosis, cell multiplication and growth is controlled by genes present in cell histone proteins comprise the large portion these genes. These histone proteins act when they are being acetylated. When these histone proteins get deacetylated they trigger apoptosis because translation of vital proteins gets stopped when they are being deacetylated and also binding capability of DNA is increased due its condensation. Studies showed that in neurodegenerative diseases deacetylation process is seemed blocked which ultimately gave rise to unchecked growth of cells which is characteristic of various kinds of carcinomas and malignancies. These findings forced scientists to discover HDAC inhibitors brought into light the process of HDAC inhibition. Quite large number of researchers described in detail the process of inhibition by administering HDAC inhibitors in clinical as well as pre-clinical trials. Different activity estimation assays are present to assess levels of HDACs. [Read the Full Post]

HISTONE DEACETYLASE INHIBITORS – CANCERS AND BEYOND

4025 | Jun 26 2012

HDAC INHIBITIORS AND EPIGENEITIC MODULATION: Histone proteins are major part of cellular genome and acetylation of these proteins plays a mile stone role in some of the most important cellular mechanisms such as growth of cell and cell death by apoptosis. The process which controls apoptosis process is carried out by checking the gene transcription of different important proteins by removing acetyl groups from histones, this deacetylation leads to condensation of DNA due to increasing capacity of DNA binding. In neurodegenerative diseases this mechanism of deacetylation goes wrong leading to various types of cancers in which cell proliferation is uncontrolled. This problem leads to the HDAC inhibitor pathway and smoothes the process of HDAC inhibition. HDAC inhibitions have been employed in preclinical and clinical studies due to which extensive and successful use of this process is targeted by many researchers. HDACs levels estimation has been developed by different activity assays. These assays are carried out by manually in the research lab or by kit methods. A nonisotopic assay that is microplate reader compatible can also be performed by researchers for the analysis of HDAC inhibitors, an appropriate test for compound profiling and robotic screening or a suitable fluorescence assay for high-throughput screening. [Read the Full Post]

VORINOSTAT: THE FAMOUS HYDROXAMIC ACID

3450 | May 15 2012

SUBEROYLANILIDE HYDROXAMIC ACID (SAHA) OR VORINOSTAT: Functions of HDACi (HDAC inhibitors) is to regulate the gene expression, induction of cell cycle arrest, stimulate apoptosis in cancer cells and modulation of various pathways in tumor cells for example cell proliferation, by hyperacetylating the histone proteins. Due to possessing these abilities, HDAC inhibitors are being used as a very valuable chemotherapeutic anti-cancer agents and SAHA or Vorinostat SAHA is important among them [1]. Vorinostat has found to be possessing strong anti-cancer properties [2] and Vorinostat structure reveals that this molecule is a derivative of hydroxamic acid. For HDAC inhibitors class I and HDACi class II Vorinostat IC50 is found to be near 50 nM. Vorinostat is soluble is ethanol up to 2 mg/ml and in DMSO 65 mg/ml but Vorinostat solubility is found to be very poor in water. [Read the Full Post]

HISTONE DEACETYLASE INHIBITORS – TUMORS AND BEYOND

3308 | May 06 2012

EPIGENETIC MODULATION BY HDAC INHIBITIORS: Acetylation process of histone proteins performs a major role in various cellular processes for example cellular growth and apoptosis by preventing the transcription of various proteins by the removal of acetyl groups from the histones hence increasing their DNA binding capacity which leads to the formation of a condensed DNA. This strategy goes wrong in case of neurodegenerative diseases and many types of cancers in which any abnormality in this process causes the removal of this block leading to the cells to proliferate in an uncontrolled manner. Then an HDAC inhibitor pathway comes into light and smoothes the progress of HDAC inhibition. The successful revelation of mechanism of HDAC inhibition has led to their extensive use in different clinical and preclinical studies. [Read the Full Post]

VORINOSTAT – AN ANTI HISTONE MODIFYING AGENT

3245 | Apr 17 2012

CHROMATIN REMODELLING INHIBITION IN CANCER THERAPY Histone modification is a very important phenomenon regarding regulation of expression of genes. Acetylation and deacetylation of histones in attached to the genetic material i.e., DNA is done with the help of specific proteins, therefore, in order to inhibit or stimulate the expression of specific genes histone tail modifying proteins can be modified. Histone deacetylating Complexes (HDACs) are one of these modifying proteins which inhibit the expression of some genes by de-acetylating them. Inhibiting these proteins may function in the modulation of gene expression by hyperacetylating them. HDAC inhibitors hence modulate the aberrant expression of genes in cancerous cells. They may inhibit cell division, arrest cell cycle or stimulate apoptosis. A lot of research is being done on different types of HDAC inhibitors in order to use them as anti-cancer therapeutics. Vorinostat is one of such HDAC inhibitors. It is also known as Suberoylanilide Hydroxamic Acid (SAHA). [Read the Full Post]

HISTONE DEACETYLASE INHIBITORS – TUMORS AND BEYOND

3032 | Apr 16 2012

EPIGENETIC MODULATION BY HDAC INHIBITIORS: Acetylation process of histone proteins performs a major role in various cellular processes for example cellular growth and apoptosis by preventing the transcription of various proteins by the removal of acetyl groups from the histones hence increasing their DNA binding capacity which leads to the formation of a condensed DNA. This strategy goes wrong in case of neurodegenerative diseases and many types of cancers in which any abnormality in this process causes the removal of this block leading to the cells to proliferate in an uncontrolled manner. Then an HDAC inhibitor pathway comes into light and smoothes the progress of HDAC inhibition. The successful revelation of mechanism of HDAC inhibition has led to their extensive use in different clinical and preclinical studies. Various assays for HDACs have been developed that are used for the analysis of HDAC levels. [Read the Full Post]

PANOBINOSTAT

4800 | Mar 19 2012

Introduction: Inhibition of HDAC Of the 18 isoforms of the histone deacetylase enzyme the class one and class two proteins are the most frequently found to be over expressed in tumor tissue. The activity of the HDAC enzyme is to remove an acetyl group from a target protein which induces a conformational change so that further protein binding is induced or inhibited. The signal begins in the cellular cytosole and is transmitted to the nucleus. This signaling transfer results eventually in the regulation of a cellular growth activity, be that life or death! The class 1 & 2 enzymes function by binding their target protein to a binding domain which has a zinc atom as a functional part. This zinc atom catalysis the deacetylation process and is the target of inhibition for most known HDAC inhibitors. [Read the Full Post]

MS-275

3530 | Mar 19 2012

Introduction: HDAC inhibition In most cancerous tissue there exists an imbalance between regulatory pathways that came be exploited for chemotherapeutic activity. One of the pathways that exhibits such activity is the acetylation / de-acetylation pathway. The regulatory enzyme in this pathway is referred to as Histone deacetylase (HDAC) and it operates in balance with Histone acetyl transferase. The addition or removal of an acetyl group causes the protein conformational shape to change and this in turn triggers either an attraction or inhibition of a protein complex formation. This action sends a signal to the nucleus to being or stop growth actions. There are many HDAC enzymes located in the cellular cytosole or within the nucleus membrane and most activity is controlled by a zinc catalyst, one small group requires NAD+ to function instead. [Read the Full Post]

HDAC INHIBITORS – CANCERS AND BEYOND

3285 | Mar 19 2012

Introduction: Histone deacetylases Cellular growth is regulated via many different mechanisms in the mammalian species, depending on the mechanism or pathway that is triggered to what effect is seen in the body. One of these regulatory compounds is called histone deacetylase or abbreviated to HDAC. As it name indicates this enzymes function is to remove an acetyl group from a target, this can be either a protein or a non-protein molecule. The removal of the acetyl group results in a conformational change in the target protein that triggers further signaling down a “pathway” that results in the induction or inhibition of carious growth related activities in the cell. HDAC is not a single protein but exists in 18 different isoforms which are classified into four groups based on their activity and physical nature. Located in the nucleus are HDAC’s 1, 2, 3 & 8 responsible for mostly transcription activities. In the cytosole are the HDAC’s 4, 5, 7 & 9, these transmit signals between extracellular sources and the nucleus. HDAC 11 and HDAC’s 6 & 10 are located in between cytosole and nucleus, their function varies. [Read the Full Post]

CUDC -101: HDAC inhibitor

3472 | Mar 20 2012

Introduction: HDAC inhibition Regulation of the activity of the proteins that initiate and transmitted signals for the cellular growth or gene transcription is a vital process in the mammalian system. There are many different mechanisms that perform this task but o of the more significant is the addition or removal of an acetyl group. The enzyme’s most responsible for this activity is known as “Histone deacetylase” and “Histone transferase” or more commonly known as HDAC and HAT respectively. In a normal situation these two enzymes operate in a balanced mechanism but genetic aberrations can significantly affect this balance in one way or another. Most typically it is observed that the HDAC is over expressed or in a permanent “on” condition in most diseased states. With over 18 currently known isoforms of HDAC divided into class’s based on the mechanism of action this represents a major target for chemotherapeutic action To target HDAC an inhibitor should be able to interfere with the ligand – enzyme binding which occurs in the tyrosine kinase domain and two classes out of 4 HDAC’s require Zinc to catalyse the reaction. [Read the Full Post]

HDAC INHIBITOR AND ITS EEFICACY IN CANCER

3053 | Mar 19 2012

Introduction: Inhibition of Histone deacetylase function Checks and balances are key terms used when describing the modulation of the cell growth pathways and quality assurance mechanisms. Verification of every stage in the process is checked for completion and there should be a balance between cell growth & cell death depending on the circumstances. Balance is maintained via the signaling pathways, which require a chemical change to transmit their signals down the line. Typically, this is the phosphorylation of the tyrosine kinase-binding domain. This domain is found in the large super family of protein kinases that dominate the regulation of cell growth. However, phosphorylation is not the only mechanism of activation, acetylation can also be utilized and this is where the histone deacetylase proteins comes into play. HDAC´s have been classified into four categories of which class 1 HDAC´s are primarily located in the nucleus, and are linked to transcriptional activation. Class 2 HDAC´s carry signals from cytosole into the nucleus were transcriptional activities are triggered. Classes 3 and 4 are not well defined and have not been associated with cancer chemotherapy or any metabolic disorders to date. [Read the Full Post]

BELINOSTAT: THE UNUSUAL HDAC INHIBITOR

4344 | Mar 13 2012

Introduction: HDAC inhibition In humans, histone deacetylase (HDAC) is a regulatory enzyme located both in the cellular cytoplasm and in the nucleus. Its function is the removal of an acetyl group from both protein and non-protein targets, this removal is usually part of a signaling pathway inducing or reducing various activities within the cell. There are currently 18 isoforms of HDAC known which are classified into four classes. Class 1 are the nucleus HDAC´s (1,2,3&8); Class II HDAC´s (4, 5, 7 & 9) are located in either the cytoplasm, the nuclease or a transitional state between the two. These two classes of enzymes are related by the fact that they require a zinc catalyst for activity. Class III (6&10) and IV HDAC´s (11) do not require zinc for their activity but instead rely on NAD+ for their activity. [Read the Full Post]

HDACs, play important roles in kidney development

5502 | Sep 08 2011

Histone deacetylases (HDACs) regulate fundamental biological processes such as cellular proliferation, differentiation, and survival via genomic and non-genomic effects. Some data suggest that HDACs may play a important role in kidney development. [Read the Full Post]

Ekwall, K. (2005). "Genome-wide analysis of HDAC function." Trends Genet 21(11): 608-615.

3350 | Apr 19 2011

This review is about genome-wide analysis of HDAC functions. It is a review of systematic study of HDACs and introduces the related targets such as Rpd3, Hos1, Hos2 , Hos3 and so on. [Read the Full Post]

de Ruijter, A. J., A. H. van Gennip, et al. (2003). "Histone deacetylases (HDACs): characterization of the classical HDAC family." Biochem J 370(Pt 3): 737-749.

3359 | Mar 20 2011

This is an article which give us the detail of HDAC family member proteins. It introduce the members of HDAC family one by one. You can make different HDACs clear after reading this article. [Read the Full Post]