HDAC4 Cancer Research Results

HDAC4, Histone deacetylases: Click to Expand ⟱
Source:
Type:
HDAC4 overexpression is associated with higher tumor grade, advanced clinical stage and poor survival. HDAC4 promotes proliferation and G1/S cell cycle progression in EC cells by inhibiting cyclin-dependent kinase (CDK) inhibitors p21 and p27 and up-regulating CDK2/4 and CDK-dependent Rb phosphorylation.

HDAC4 is often overrepresented and associated with poor prognosis.
HDAC Inhibitors: Given the role of HDAC4 in cancer, HDAC inhibitors (HDACi) are being explored as potential therapeutic agents.
Scientific Papers found: Click to Expand⟱
2974- CUR,    Curcumin Suppresses Metastasis via Sp-1, FAK Inhibition, and E-Cadherin Upregulation in Colorectal Cancer
- in-vitro, CRC, HCT116 - in-vitro, CRC, HT29 - in-vitro, CRC, HCT15 - in-vitro, CRC, COLO205 - in-vitro, CRC, SW-620 - in-vivo, NA, NA
TumCMig↓, Curcumin significantly inhibits cell migration, invasion, and colony formation in vitro and reduces tumor growth and liver metastasis in vivo.
TumCI↓,
TumCG↓,
TumMeta↓,
Sp1/3/4↓, curcumin suppresses Sp-1 transcriptional activity and Sp-1 regulated genes including ADEM10, calmodulin, EPHB2, HDAC4, and SEPP1 in CRC cells.
HDAC4↓,
FAK↓, Curcumin inhibits focal adhesion kinase (FAK) phosphorylation
CD24↓, Curcumin reduces CD24 expression in a dose-dependent manner in CRC cells
E-cadherin↑, E-cadherin expression is upregulated by curcumin and serves as an inhibitor of EMT.
EMT↓,
TumCP↓,
NF-kB↓, CUR prevents cancer cells migration, invasion, and metastasis through inhibition of PKC, FAK, NF-κB, p65, RhoA, MMP-2, and MMP-7 gene expressions
AP-1↝,
STAT3↓, downregulation of CD24 reduces STAT and FAK activity, decreases cell proliferation, metastasis in human tumor
P53?,
β-catenin/ZEB1↓, CUR could activate protein kinase D1 (PKD1) suggesting that suppressing of β-catenin transcriptional activity prevents growth of prostate cancer
NOTCH1↝,
Hif1a↝,
PPARα↝,
Rho↓, CUR prevents cancer cells migration, invasion, and metastasis through inhibition of PKC, FAK, NF-κB, p65, RhoA, MMP-2, and MMP-7 gene expressions
MMP2↓,
MMP9↓,

3233- EGCG,    Epigallocatechin gallate inhibits HeLa cells by modulation of epigenetics and signaling pathways
- in-vitro, Cerv, HeLa
DNMTs↓, EGCG may competitively inhibit some epigenetic enzymes (DNMT1, DNMT3A, HDAC2, HDAC3, HDAC4, HDAC7 and EZH2).
DNMT1↓,
DNMT3A↓,
HDAC2↓,
HDAC3↓,
HDAC4↓,
EZH2↓, Interaction of EGCG with EZH2 protein indicates inhibition of activity
PI3K↓, Downregulation of key signaling moieties of PI3K, Wnt and MAPK pathways
Wnt↓,
MAPK↓,
hTERT/TERT↓, including TERT, CCNB1, CCNB2, MMP2, MMP7. PIK3C2B, PIK3CA, MAPK8 and IL6 was also observed
MMP2↓,
MMP7↓,
IL6↓,
MDM2↓, Fig 1
MMP-10↓,
TP53↑,
PTEN↑,

76- QC,    Multifaceted preventive effects of single agent quercetin on a human prostate adenocarcinoma cell line (PC-3): implications for nutritional transcriptomics and multi-target therapy
- in-vitro, Pca, PC3
aSmase↝, Figure 3b shows that quercetin treatment caused a dose-dependent augmentation in mRNA levels of Diablo and FAS
Diablo↑,
Fas↓,
Hsc70↓, coupled with a dose-responsive reduction in transcriptional activity of HSC70, HIF1A, Mcl-1, Hsp90 and BIRC4.
Hif1a↓,
Mcl-1↓,
HSP90↓,
FLT4↓, A dose-dependent drop in mRNA levels of FLT4, EPHB4, DNAPK, PARP1, ATM, perlecan, GnTV and heparanase genes was observed after treatment of PC-3 cells with quercetin
EphB4↓,
DNA-PK↓,
PARP1↓,
ATM↓,
XIAP↝,
PLC↓,
GnT-V↝,
heparanase↝,
NM23↑, quercetin significantly exerted a dose-responsive rise in transcriptional levels of NM23 and CSR1 genes
CSR1↑,
SPP1↓, coupled with an expressive lowering in mRNA levels of SPP1, DNMT1, HDAC4, CXCR4, b-catenin and NHE1.
DNMT1↓,
HDAC4↓,
CXCR4↓,
β-catenin/ZEB1↓,
FBXW7↝,
AMACR↓,
cycD1/CCND1↓,
IGF-1R↓, down-regulation of mRNA levels of AMACR, cyclin D1, NOS2A, IGF1R, IMPDH1, IMPDH2 and HEC1
IMPDH1↓,
IMPDH2↓,
HEC1↓,
NHE1↓,
NOS2↓,

5027- QC,    NRF2 Is Targeted By the Polyphenol Quercetin and Induces Apoptosis, in Part, through up Regulation of Pro Apoptotic Mirs
- in-vivo, AML, NA
HDAC4↓, Qu treatment (50 µM Qu) for 48h downregulated HDAC4, NRF2 and p-NRF2 at protein levels (p<0.05; p<0.005; p<0.005 respectively).
NRF2↓,
p‑NRF2↓,
miR-133a-3p↑, miR-1, miR-133a/b, which target anti-apoptotic genes and miR-206, a pro apoptotic miR, were validated in xenograft model samples, resulting in a significant up-regulation of the expression levels in treated animals
miR-206↑,

2445- SFN,    Sulforaphane-Induced Cell Cycle Arrest and Senescence are accompanied by DNA Hypomethylation and Changes in microRNA Profile in Breast Cancer Cells
- in-vitro, BC, MCF-7 - in-vitro, BC, MDA-MB-231 - in-vitro, BC, SkBr3
TumCCA↑, SFN (5-10 µM) promoted cell cycle arrest, elevation in the levels of p21 and p27 and cellular senescence
P21↑,
p27↑,
NO↑, effects were accompanied by nitro-oxidative stress, genotoxicity and diminished AKT signaling
Akt↓,
ATP↓, decreased pools of ATP and AMPK activation, and autophagy induction
AMPK↑,
TumAuto↑,
DNMT1↓, decreased levels of DNA methyltransferases (DNMT1, DNMT3B)
HK2↓, A decrease in HK2 levels was observed in SFN-treated MDA-MB-231 cells
PKM2↓, and a decrease in PKM2 levels was noticed in SFN-treated MDA-MB-231 and SK-BR-3 cells
HDAC3↓, . In contrast, HDAC3 , HDAC4 , HDAC6 , HDAC7 , HDAC8 ), HDAC9 and HDAC10 (histone deacetylase 10) mRNA levels were decreased in SFN-treated MDA-MB-231 cells
HDAC4↓,
HDAC8↓,

3424- TQ,    Thymoquinone Is a Multitarget Single Epidrug That Inhibits the UHRF1 Protein Complex
- Review, Var, NA
DNMT1↓, In this review, we highlight TQ as a potential multitarget single epidrug that functions by targeting the UHRF1/DNMT1/HDAC1/G9a complex
HDAC1↓,
TumCCA↑, inhibition of cell division, promotion of cell cycle arrest, activation of ROS production, induction of apoptosis and inhibition of tumor angiogenesis and metastasis
ROS↑,
Apoptosis↑,
angioG↓,
TumMeta↓,
selectivity↑, When compared to its effects on cancer cells, TQ has no or only mild cytotoxic effects on matched normal cells, such as normal human fibroblast cells [
BioAv↓, poor pharmacokinetics and chemical stability of TQ
BioAv↓, TQ is heat and light-sensitive, and it has poor solubility in aqueous media, which affects its biodistribution
HDAC1↓, T-ALL TQ decreased in the expression of HDAC1, 4 and 9
HDAC4↓,
UHRF1↓, TQ induces auto-ubiquitination of UHRF1 and subsequent degradation in cancer cells [23] by targeting its RING domain, which is the only domain of the UHRF1 structure that exhibits enzymatic activity
selectivity↑, via a specific inhibition of UHRF1 expression levels in cancer cells without affecting its expression in normal human cells.
G9a↓, TQ could quite possibly inhibit G9a and/or delocalize it from chromatin through its effects on UHRF1.

3426- TQ,    Thymoquinone-Induced Reactivation of Tumor Suppressor Genes in Cancer Cells Involves Epigenetic Mechanisms
- in-vitro, BC, MDA-MB-468 - in-vitro, AML, JK
UHRF1↓, (UHRF1), DNMT1,3A,3B, G9A, HDAC1,4,9, KDM1B, and KMT2A,B,C,D,E, were downregulated in TQ-treated Jurkat cells
DNMT1↓,
DNMT3A↓,
DNMTs↓,
HDAC1↓,
HDAC4↓,
HDAC↓,
DLC1↑, several TSGs, such as DLC1, PPARG, ST7, FOXO6, TET2, CYP1B1, SALL4, and DDIT3, known to be epigenetically silenced in various tumors, including acute leukemia, were upregulated,
PPARγ↑,
FOXO↑,
TET2↑,
CYP1B1↑,
G9a↓, expression of UHRF1, DNMT1, G9a, and HDAC1 genes in both cancer cell (Jurkat cells and MDA-MB-468 cells) lines depends on the TQ dose

3423- TQ,    Epigenetic role of thymoquinone: impact on cellular mechanism and cancer therapeutics
- Review, Var, NA
AntiCan↑, Thymoquinone is a natural product with anticancer activity.
Inflam↓, Thymoquinone has been shown to exert anti-inflammatory, antidiabetic, antihypertensive, antimicrobial, analgesic, immunomodulatory, spasmolytic, hepatoprotective, renal-protective, gastroprotective, bronchodilatory, antioxidant and antineoplastic eff
hepatoP↑,
RenoP↑,
BAX↑, Thymoquinone can upregulate proapoptotic genes and proteins, such as Bax/Bak, or downregulate antiapoptotic genes and proteins, such as Bcl-2, Bcl-xL, among others, as well as modulating the caspase pathway
Bak↑,
Bcl-2↓,
Bcl-xL↓,
ROS↑, through the generation of reactive oxygen species (ROS)
P53↑, overexpressed or activated by thymoquinone; for example, p53, PTEN, p21, p27 and breast cancer type 1 susceptibility protein (BRCA1), among others,
PTEN↑,
P21↑,
p27↑,
BRCA1↑,
PI3K↓, (PI3K)/Akt and mitogen-activated protein kinase (MAPK)/ERK, have been found to be inhibited by thymoquinone
Akt↓,
MAPK↓,
ERK↓,
p‑ERK↓, thymoquinone reduces ERK phosphorylation and matrix metalloproteinase (MMP) secretion by downregulating focal adhesion kinase (FAK)
MMPs↓,
FAK↓,
Twist↓, downregulates Twist1 and Zeb1 transcription factors, and thus inhibits epithelial to mesenchymal transition (EMT) and subsequently inhibits cancer metastasis
Zeb1↓,
EMT↓,
TumMeta↓,
angioG↓, thymoquinone can inhibit angiogenesis by interfering with essential steps of neovascularization, such as suppressing proangiogenic vascular endothelial growth factor (VEGF)
VEGF↓,
HDAC↓, HDACs are usually overexpressed in MCF-7 breast cancer cells, and thymoquinone can act as a HDAC inhibitor (HDACi) that potently induces apoptosis through inducing acetylation of histones and inhibiting deacetylation of histones.
Maspin↑, thymoquinone reactivates HDAC target genes (p21 and Maspin), inducing the upregulation of Bax
SIRT1↑, thymoquinone can upregulate SIRT1 expression in neonatal rat cardiomyocytes and consequently deacetylates p53; thus, it can act as an apoptosis inducer
DNMT1↓, Collectively, they suggested that thymoquinone induces methylation of DNA via binding with DNMT1 and suppressing its expression,
DNMT3A↓, thymoquinone decreases the expression of some important epigenetic proteins like DNMT1,3A,3B, G9A, HDAC1,4,9, KDM1B, KMT2A,B,C,D,E and UHRF1 in Jurkat cells,
HDAC1↓,
HDAC4↓,


Showing Research Papers: 1 to 8 of 8

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 8

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

NRF2↓, 1,   p‑NRF2↓, 1,   ROS↑, 2,  

Mitochondria & Bioenergetics ⓘ

ATP↓, 1,   XIAP↝, 1,  

Core Metabolism/Glycolysis ⓘ

AMACR↓, 1,   AMPK↑, 1,   HK2↓, 1,   PKM2↓, 1,   PPARα↝, 1,   PPARγ↑, 1,   SIRT1↑, 1,  

Cell Death ⓘ

Akt↓, 2,   Apoptosis↑, 1,   aSmase↝, 1,   Bak↑, 1,   BAX↑, 1,   Bcl-2↓, 1,   Bcl-xL↓, 1,   CSR1↑, 1,   Diablo↑, 1,   Fas↓, 1,   hTERT/TERT↓, 1,   MAPK↓, 2,   Mcl-1↓, 1,   MDM2↓, 1,   p27↑, 2,  

Kinase & Signal Transduction ⓘ

Sp1/3/4↓, 1,  

Transcription & Epigenetics ⓘ

EZH2↓, 1,   SPP1↓, 1,  

Protein Folding & ER Stress ⓘ

Hsc70↓, 1,   HSP90↓, 1,  

Autophagy & Lysosomes ⓘ

TumAuto↑, 1,  

DNA Damage & Repair ⓘ

ATM↓, 1,   BRCA1↑, 1,   CYP1B1↑, 1,   DNA-PK↓, 1,   DNMT1↓, 6,   DNMT3A↓, 3,   DNMTs↓, 2,   G9a↓, 2,   P53?, 1,   P53↑, 1,   PARP1↓, 1,   TP53↑, 1,   UHRF1↓, 2,  

Cell Cycle & Senescence ⓘ

cycD1/CCND1↓, 1,   P21↑, 2,   TumCCA↑, 2,  

Proliferation, Differentiation & Cell State ⓘ

CD24↓, 1,   EMT↓, 2,   ERK↓, 1,   p‑ERK↓, 1,   FBXW7↝, 1,   FOXO↑, 1,   HDAC↓, 2,   HDAC1↓, 4,   HDAC2↓, 1,   HDAC3↓, 2,   HDAC4↓, 8,   HDAC8↓, 1,   IGF-1R↓, 1,   NOTCH1↝, 1,   PI3K↓, 2,   PTEN↑, 2,   STAT3↓, 1,   TumCG↓, 1,   Wnt↓, 1,  

Migration ⓘ

AP-1↝, 1,   DLC1↑, 1,   E-cadherin↑, 1,   EphB4↓, 1,   FAK↓, 2,   GnT-V↝, 1,   heparanase↝, 1,   miR-133a-3p↑, 1,   miR-206↑, 1,   MMP-10↓, 1,   MMP2↓, 2,   MMP7↓, 1,   MMP9↓, 1,   MMPs↓, 1,   NM23↑, 1,   Rho↓, 1,   TumCI↓, 1,   TumCMig↓, 1,   TumCP↓, 1,   TumMeta↓, 3,   Twist↓, 1,   Zeb1↓, 1,   β-catenin/ZEB1↓, 2,  

Angiogenesis & Vasculature ⓘ

angioG↓, 2,   FLT4↓, 1,   Hif1a↓, 1,   Hif1a↝, 1,   NO↑, 1,   VEGF↓, 1,  

Barriers & Transport ⓘ

NHE1↓, 1,  

Immune & Inflammatory Signaling ⓘ

CXCR4↓, 1,   IL6↓, 1,   Inflam↓, 1,   NF-kB↓, 1,  

Cellular Microenvironment ⓘ

PLC↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 2,   selectivity↑, 2,   TET2↑, 1,  

Clinical Biomarkers ⓘ

BRCA1↑, 1,   EZH2↓, 1,   HEC1↓, 1,   hTERT/TERT↓, 1,   IL6↓, 1,   Maspin↑, 1,   NOS2↓, 1,   TP53↑, 1,  

Functional Outcomes ⓘ

AntiCan↑, 1,   hepatoP↑, 1,   IMPDH1↓, 1,   IMPDH2↓, 1,   RenoP↑, 1,  
Total Targets: 119

Pathway results for Effect on Normal Cells:


Total Targets: 0

Scientific Paper Hit Count for: HDAC4, Histone deacetylases
3 Thymoquinone
2 Quercetin
1 Curcumin
1 EGCG (Epigallocatechin Gallate)
1 Sulforaphane (mainly Broccoli)
Query results interpretion may depend on "conditions" listed in the research papers.
Such Conditions may include : 
  -low or high Dose
  -format for product, such as nano of lipid formations
  -different cell line effects
  -synergies with other products 
  -if effect was for normal or cancerous cells

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