HDAC2 Cancer Research Results

HDAC2, Histone Deacetylase 2: Click to Expand ⟱

Source:

Type:

HDAC2 is a member of the class I histone deacetylase family that removes acetyl groups from lysine residues on histone proteins.

• This deacetylation usually promotes chromatin compaction, leading to transcriptional repression of genes involved in cell differentiation, apoptosis, and cell cycle regulation.
• HDAC2, along with its relatives HDAC1 and others, is often found as part of multiprotein corepressor complexes that regulate gene expression in both normal and cancer cells.

2. Role of HDAC2 in Cancer
• Overexpression and Dysregulation:
– In several types of cancer, HDAC2 is overexpressed or dysregulated, contributing to an altered transcriptional profile.
– Elevated HDAC2 levels can lead to the suppression of tumor suppressor genes and genes involved in cell-cycle checkpoints or apoptosis, facilitating tumor progression.

• Impact on the Tumor Microenvironment:
– HDAC2 activity influences not only tumor cells but also the surrounding stromal and immune cells, affecting inflammatory responses and immune evasion strategies.

Scientific Papers found: Click to Expand⟱

1224-

Buty,

Intratumor microbiome-derived butyrate promotes lung cancer metastasis

in-vivo,

Lung,

TumCG↑, We prove that intratumor injection of butyrate-producing bacteria Roseburia can promote subcutaneous tumor growth
H19↑,
HDAC2↓,

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↑,

5227-

EMD,

Emodin and emodin-rich rhubarb inhibits histone deacetylase (HDAC) activity and cardiac myocyte hypertrophy

vitro+vivo,

Nor,

angiotensin II (Ang) mouse model of cardiac hypertrophy and fibrosis and are linked to HDAC inhibition.

*cardioP↑, Emodin is an anthraquinone that has been implicated in cardiac protection.
HDAC↓, Emodin and emodin-rich rhubarb inhibited HDAC activity in a dose-dependent, fast-on/slow-off manner
HDAC1↓, inhibited class I and II HDAC activity in a dose-dependent manner (IC50=100 mg/L,
HDAC2↓,
ac‑H3↑, emodin increased histone H3 acetylation on lysine residues
Dose↝, we would speculate that rhubarb need not be ingested frequently for HDAC inhibition. we would argue that an emodin dietary supplement could also be considered for HDAC inhibition
BioAv↓, emodin bioavailability remains low

1065-

GA,

Gallic acid, a phenolic acid, hinders the progression of prostate cancer by inhibition of histone deacetylase 1 and 2 expression

vitro+vivo,

Pca,

mice

tumCV↓, GA decreased the cell viability of only PCa cell lines and not normal cells (contrary to another HDAC inhibitor, suberoylanilide hydroxamic acid) ****
MMP↓,
DNAdam↑,
HDAC1↓,
HDAC2↓,
PCNA↓,
cycD1/CCND1↓,
cycE1↓,
P21↑, up-regulating the expression of cell cycle arrest gene p21
TumVol↓, mice

1435-

GEN,

SFN,

The Effects of Combinatorial Genistein and Sulforaphane in Breast Tumor Inhibition: Role in Epigenetic Regulation

in-vitro,

BC,

MDA-MB-231

in-vitro,

BC,

MCF-7

DNMTs↓, GEN extensively studied for its role as DNA methyltransferase (DNMT) inhibitor
HDAC↓, SFN), is known as a histone deacetylase (HDAC) inhibitor
eff↑, Our results indicate that the combination of GEN and SFN is much more effective than their single doses in increasing the rate of apoptosis
TumCCA↑, G2 phase in MDA-MB-231 and G1 phase in MCF-7
HMTs↓, histone methyltransferase (HMT) inhibitor
HDAC2↓, combination downregulates the levels of HDAC2 and HDAC3 both at the mRNA and protein levels
HDAC3↓,
KLF4↓, potential to downregulate KLF4 levels, which plays an important role in stem cell formation.
hTERT/TERT↓,

4293-

LT,

HDAC2-and-Tau?redirectedFrom=fulltext">Regulatory Role of NF-κB on HDAC2 and Tau Hyperphosphorylation in Diabetic Encephalopathy and the Therapeutic Potential of Luteolin

in-vivo,

Diabetic,

 90 mice were given a high-fat die

*Inflam↓, luteolin, a natural flavonoid compound with anti-inflammatory, antioxidant, and neuroprotective properties.
*antiOx↑,
*neuroP↑,
*cognitive↑, results indicated that treatment with luteolin improved the degree of cognitive impairment in mice with DE.
*p‑mTOR↓, decreased the levels of phosphorylated mTOR, phosphorylated NF-κB, and histone deacetylase 2 (HDAC2) and increased the expression of brain-derived neurotrophic factor and synaptic-related proteins
*p‑NF-kB↓,
*HDAC2↓,
*BDNF↑,
*other↓, luteolin may also directly target HDAC2, as an HDAC2 inhibitor, to alleviate DE, complementing mTOR/NF-κB signaling inhibition
*p‑tau↓, HDAC2 and tau hyperphosphorylation are regulated by the mTOR/NF-κB signaling cascade in DE, and luteolin is found to reverse these effects, demonstrating its protective role in DE

4643-

OLE,

HT,

Use of Oleuropein and Hydroxytyrosol for Cancer Prevention and Treatment: Considerations about How Bioavailability and Metabolism Impact Their Adoption in Clinical Routine

Review,

Var,

TumCCA↑, A similar S phase cell cycle arrest was also observed for 800 μM HT, and induction of apoptosis also took place after 24 h incubation of HT-29 cells with 600 μM and 800 μM HT
Apoptosis↑,
ER Stress↑, 400 μM HT triggered endoplasmic reticulum stress in HT-29 cells, with activation of unfolded protein response,
UPR↑,
CHOP↑, increase in CHOP protein levels (responsible for ROS production and Bcl-2 downregulation) and NADPH oxidase 4 (NOX4)
ROS↑,
Bcl-2↓,
NOX4↑,
Hif1a↓, Moreover, 400 μM HT reduced HIF-1α protein levels
MMP2↓, figure 2
MMP↓,
VEGF↓,
Akt↓,
NF-kB↓,
p65↓,
SIRT3↓,
mTOR↓,
Catalase↓,
SOD2↓,
FASN↓,
STAT3↓,
HDAC2↓,
HDAC3↓,
BAD↑, figure 2 upregulated
BAX↑,
Bak↑,
Casp3↑,
Casp9↑,
PARP↑,
P53↑,
P21↑,
p27↑,
Half-Life↝, HT added to extra virgin olive oil produced a plasma peak of 3.79 ng/mL after 30 min, followed by a rapid decline in HT plasma concentration
BioAv↓, On the basis of these pieces of data, it becomes evident that cytotoxicity and anti-cancer effects of OLE and HT were recorded at concentrations largely exceeding those reachable with diet/olive oil consumption
BioAv↓, Thus, it is difficult to imagine how OLE and HT may be used as cancer-preventive/treating agents if the route of administration is ingestion.
selectivity↑, However, even at high concentrations, OLE and HT seem to be selectively cytotoxic for cancer cells, with no or negligible/minimal effects on non-cancer cells,
RadioS↑, 200 μM OLE enhanced cell radiosensitivity in vitro and in vivo after injection in BALB/C nude mice
*ROS↓, A lot of experimental data in vivo and in vitro have definitively demonstrated the ROS scavenger ability of OLE and HT, which can also act on antioxidant cellular mechanisms restoring ROS homeostasis,
*GSH↑, including promotion of the increase in reduced glutathione levels (GSH), depletion of lipid peroxidation product malondialdehyde (MDA), intensification of the expression and/or activity of detoxicating enzymes SOD, CAT, glutathione-S-transferase (GST
*MDA↓,
*SOD↑,
*Catalase↑,
*NRF2↑, and nuclear factor E2-related factor 2 (Nrf2) upregulation/transactivation,
*chemoP↑, OLE and HT have shown an important ability to mitigate the toxicity elicited by chemotherapeutic agents mainly through their largely demonstrated antioxidant and ROS scavenger activity.
*Inflam↓, OLE and HT exhibit an anti-inflammatory activity that has been demonstrated in multiple in vivo and in vitro models,
PPARγ↑, HT-dependent anti-inflammatory effect was also mediated by HT-elicited increase in protein levels of PPARγ

1676-

PBG,

Use of Stingless Bee Propolis and Geopropolis against Cancer—A Literature Review of Preclinical Studies

Review,

Var,

20-250ug/mL

ROS↑, evidenced in the accumulation of reactive oxygen species (ROS)
MMP↓, reduction of mitochondrial membrane potential (Δψm)
Bcl-2↓, decreased levels of Bcl-2 proteins (antiapoptotic proteins) and AKT-3
eff↑, combination of the extract (30 µg/mL) with the antineoplastic vemurafenib (15 μM) against melanoma cells demonstrated a synergistic effect
tumCV↓, decreased cell viability for 23% of the colon cancer cells (SW620) treated with the aqueous propolis extract produced by Trigona laeviceps
TumCCA↑, antitumor activity of artepillin C is mediated by one of the following mechanisms: induction of cell cycle arrest in cancer cells, inhibition of angiogenesis, and inhibition of the oncogenic PAK1 signaling cascade
angioG↓,
PAK1↓,
HDAC1↓, negatively regulated expression of histone deacetylases (HDAC) 1 and 2
HDAC2↓,
P53↑, positive regulation of acetyl-p53 expression at the protein level
PCNA↓, negative regulation of cell-cycle-related gene expression, i.e., proliferating cell nuclear antigen (PCNA) and cyclin D1 and E1
cycD1/CCND1↓,
cycE/CCNE↓,
P21?, positively regulating the expression of the cell cycle arrest gene p21
BAX↑, Bax, Bcl-2, cleaved caspase-3, and poly(ADP-ribose) polymerase
cl‑Casp3↑,
cl‑PARP↑,
ChemoSen↑, apigenin significantly down-regulates Mcl-1 transcription and translation levels in SKOV3 and SKOV3/DDP cells, which is responsible for its cytotoxic functions and chemosensitizing effects

3359-

QC,

Quercetin modifies 5′CpG promoter methylation and reactivates various tumor suppressor genes by modulating epigenetic marks in human cervical cancer cells

in-vitro,

Cerv,

HeLa

DNMTs↓, When nuclear extracts were incubated with increasing doses of quercetin (25 and 50uM) they were found to inhibit the function of the DNMTs by 32% and 49% respectively, in comparison to untreated control
HDAC↓, quercetin (25 and 50 uM), they were found to inhibit the function of the HDACs by 47% and 62% in comparison to untreated control.
HMTs↓, quercetin (25 and 50 uM), were found to inhibit the function of the HMT H3K9 by 63% and 71%
DNMT3A↓, preferred binding of quercetin on DNMT3A and DNMT3B is within the substrate binding cavity and could competitively inhibit the protein
EZH2↓, Quercetin interacts with EZH2 and functions as an inhibitor
HDAC1↓, Quercetin was able to reduce the activity of class II HDACs significantly, with concomitant downregulation of HDAC1, HDAC2, HDAC6, HDAC7, and HDAC11 expression
HDAC2↓,
HDAC6↓,
HDAC11↓,
G9a↓, quercetin and this correlates well with the observed downregulation of G9A expression
TIMP3↑, Fig8: quercetin resulted in reduced promoter methylation of several TSGs (APC, CDH1, CDH13, DAPK1, FHIT, GSTP1, MGMT, MLH1, PTEN, RARB, RASSF1, SOC51, TIMP3, and VHL
PTEN↑,
SOCS1↑,

1748-

RosA,

The Role of Rosmarinic Acid in Cancer Prevention and Therapy: Mechanisms of Antioxidant and Anticancer Activity

Review,

Var,

AntiCan↑, RA exhibits significant potential as a natural agent for cancer prevention and treatment
*BioAv↝, Various factors, including its lipophilic nature, stability in the gastrointestinal tract, and interactions with food, can significantly influence its absorption
*CardioT↓, RA attenuated these effects by reducing ROS levels, indicating its potential role as a cardioprotective agent during chemotherapy.
*Iron↓, Another significant mechanism antioxidant activity of RA is its capacity to chelate transition metal ions, particularly iron (Fe2+) and copper (Cu2+), which can catalyze the formation of highly reactive hydroxyl radicals through the Fenton reaction.
*ROS↓, forming stable complexes with Fe2+ and Cu2+, thus inhibiting their pro-oxidant activity.
*SOD↑, SOD, CAT, and GPx, play crucial roles in neutralizing ROS and maintaining cellular redox homeostasis. RA upregulates the expression and activity of these enzymes
*Catalase↑,
*GPx↑,
*NRF2↑, activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, a primary regulator of the antioxidant response
MARK4↓, Anwar’s study demonstrated that RA inhibited MARK4 activity in MDA-MB-231 breast cancer cells, resulting in dose-dependent apoptosis
MMP9↓, RA effectively inhibited cancer cell invasion and migration by reducing matrix metalloproteinase-9 (MMP-9) activity
TumCCA↑, caused cell cycle arrest
Bcl-2↓, RA downregulates Bcl-2 expression and upregulates Bax, thereby promoting apoptosis
BAX↑,
Apoptosis↑,
E-cadherin↑, promoting E-cadherin expression, while downregulating N-cadherin and vimentin
N-cadherin↓,
Vim↓,
Gli1↓, induced apoptosis by downregulating Gli1, a key component of the Hedgehog signaling pathway,
HDAC2↓, RA induced apoptosis by modulating histone deacetylase 2 (HDAC2) expression
Warburg↓, anti-Warburg effect of RA in colorectal carcinoma
Hif1a↓, RA inhibits hypoxia-inducible factor-1 alpha (HIF-1α) and downregulates miR-155
miR-155↓,
p‑PI3K↑, RA has been shown to upregulate p-PI3K, protecting cells through the PI3K/Akt pathway,
ROS↑, RA, induces significant ROS generation in A549 cells, which triggers both apoptosis and autophagy.
*IronCh↑, RA’s dual nature as both a phenolic acid and a flavonoid-related compound enables it to chelate metal ions and prevent the formation of free radicals,

3003-

RosA,

Comprehensive Insights into Biological Roles of Rosmarinic Acid: Implications in Diabetes, Cancer and Neurodegenerative Diseases

Review,

Var,

Review,

AD,

Review,

Park,

*Inflam↓, anti-inflammatory and antioxidant properties and its roles in various life-threatening conditions, such as cancer, neurodegeneration, diabetes,
*antiOx↑,
*neuroP↑,
*IL6↓, diabetic rat model treated with RA, there is an anti-inflammatory activity reported. This activity is achieved through the inhibition of the expression of various proinflammatory factors, including in IL-6, (IL-1β), tumour
*IL1β↓,
*NF-kB↓, inhibiting NF-κB activity and reducing the production of prostaglandin E2 (PGE2), nitric oxide (NO), and cyclooxygenase-2 (COX-2) in RAW 264.7 cells.
*PGE2↓,
*COX2↓,
*MMP↑, RA inhibits cytotoxicity in tumour patients by maintaining the mitochondrial membrane potential
*memory↑, amyloid β(25–35)-induced AD in rats was treated with RA, which mitigated the impairment of learning and memory disturbance by reducing oxidative stress
*ROS↓,
*Aβ↓, daily consumption of RA diminished the effect of neurotoxicity of Aβ25–35 in mice
*HMGB1↓, SH-SY5Y in vitro and ischaemic diabetic stroke in vivo, and the studies revealed that a 50 mg/kg dose of RA decreased HMGB1 expression
TumCG↓, Rosemary and its extracts have been shown to exhibit potential in inhibiting the growth of cancer cells and the development of tumours in various cancer types, including colon, breast, liver, and stomach cancer
MARK4↓, Another study reported the inhibition of Microtubule affinity regulating kinase 4 (MARK4) by RA
Zeb1↓, Fig 4 BC:
MDM2↓,
BNIP3↑,
ASC↑, Skin Cancer
NLRP3↓,
PI3K↓,
Akt↓,
Casp1↓,
E-cadherin↑, Colon Cancer
STAT3↓,
TLR4↓,
MMP↓,
ICAM-1↓,
AMPK↓,
IL6↑, PC and GC
MMP2↓,
Warburg↓,
Bcl-xL↓, CRC: Apoptosis induction caspases ↑, Bcl-XL ↓, BCL-2 ↓, Induces cell cycle arrest, Inhibition of EMT and invasion, Reduced metastasis
Bcl-2↓,
TumCCA↑,
EMT↓,
TumMeta↓,
mTOR↓, Inhibits mTOR/S6K1 pathway to induce apoptosis in cervical cancer
HSP27↓, Glioma ↓ expression of HSP27 ↑ caspase-3
Casp3↑,
GlucoseCon↓, GC: Inhibited the signs of the Warburg effect, such as high glucose consumption/anaerobic glycolysis, lactate production/cell acidosis, by inhibiting the IL-6/STAT3 pathway
lactateProd↓,
VEGF↓, ↓ angiogenic factors (VEGF) and phosphorylation of p65
p‑p65↓,
GIT1↓, PC: Increased degradation of Gli1
FOXM1↓, inhibiting FOXM1
cycD1/CCND1↓, RA treatment in CRC cells inhibited proliferation-induced cell cycle arrest of the G0/G1 phase by reducing the cyclin D1 and CDK4 levels,
CDK4↓,
MMP9↓, CRC cells, and it led to a decrease in the expressions of matrix metalloproteinase (MMP)-2 and MMP-9.
HDAC2↓, PCa cells through the inhibition of HDAC2

3001-

RosA,

Therapeutic Potential of Rosmarinic Acid: A Comprehensive Review

Review,

Var,

TumCP↓, including in tumor cell proliferation, apoptosis, metastasis, and inflammation
Apoptosis↑,
TumMeta↓,
Inflam↓,
*antiOx↑, RA is therefore considered to be the strongest antioxidant of all hydroxycinnamic acid derivatives
*AntiAge↑, , it also exerts powerful antimicrobial, anti-inflammatory, antioxidant and even antidepressant, anti-aging effects
*ROS↓, RA and its metabolites can directly neutralize reactive oxygen species (ROS) [10] and thereby reduce the formation of oxidative damage products.
BioAv↑, RA is water-soluble, and according to literature data, the efficacy of secretion of this compound in infusions is about 90%
Dose↝, Accordingly, it is possible to consume approximately 110 mg RA daily, i.e., approximately 1.6 mg/kg for adult men weighing 70 kg.
NRF2↑, liver cancer cell line, HepG2, transfected with plasmid containing ARE-luciferin gene, RA predominantly enhances ARE-luciferin activity and promotes nuclear factor E2-related factor-2 (Nrf2) translocation from cytoplasm to the nucleus
P-gp↑, and also increases MRP2 and P-gp efflux activity along with intercellular ATP level
ATP↑,
MMPs↓, RA concurrently induced necrosis and apoptosis and stimulated MMP dysfunction activated PARP-cleavage and caspase-independent apoptosis.
cl‑PARP↓,
Hif1a↓, inhibits transcription factor hypoxia-inducible factor-1α (HIF-1α) expression
GlucoseCon↓, it also suppressed glucose consumption and lactate production in colorectal cells
lactateProd↓,
Warburg↓, may suppress the Warburg effects through an inflammatory pathway involving activator of transcription-3 (STAT3) and signal transducer of interleukin (IL)-6
TNF-α↓, RA supplementation also reduced tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2) and IL-6 levels, and modulated p65 expression [
COX2↓,
IL6↓,
HDAC2↓, RA induced the cell cycle arrest and apoptosis in prostate cancer cell lines (PCa, PC-3, and DU145) [31]. These effects were mediated through modulation of histone deacetylases expression (HDACs), specifically HDAC2;
GSH↑, RA can also inhibit adhesion, invasion, and migration of Ls 174-T human colon carcinoma cells through enhancing GSH levels and decreasing ROS levels
ROS↓,
ChemoSen↑, RA also enhances chemosensitivity of human resistant gastric carcinoma SGC7901 cells
*BG↓, RA significantly increased insulin index sensitivity and reduced blood glucose, advanced glycation end-products, HbA1c, IL-1β, TNFα, IL-6, p-JNK, P38 mitogen-activated protein kinase (MAPK), and NF-κB levels
*IL1β↓,
*TNF-α↓,
*IL6↓,
*p‑JNK↓,
*p38↓,
*Catalase↑, The reduced activities of CAT, SOD, glutathione S-transferases (GST), and glutathione peroxidase (GPx) and the reduced levels of vitamins C and E, ceruloplasmin, and GSH in plasma of diabetic rats were also significantly recovered by RA application
*SOD↑,
*GSTs↑,
*VitC↑,
*VitE↑,
*GSH↑,
*GutMicro↑, protective effects of RA (30 mg/kg) against hypoglycemia, hyperlipidemia, oxidative stress, and an imbalanced gut microbiota architecture was studied in diabetic rats.
*cardioP↑, Cardioprotective Activity: RA also reduced fasting serum levels of vascular cell adhesion molecule 1 (VCAM-1), inter-cellular adhesion molecule 1 (ICAM-1), plasminogen-activator-inhibitor-1 (PAI-1), and increased GPX and SOD levels
*ROS↓, Finally, in H9c2 cardiac muscle cells, RA inhibited apoptosis by decreasing intracellular ROS generation and recovering mitochondria membrane potential
*MMP↓,
*lipid-P↓, At once, RA suppresses lipid peroxidation (LPO) and ROS generation, whereas in HSC-T6 cells it increases cellular GSH.
*NRF2↑, Additionally, it significantly increases Nrf2 translocation
*hepatoP↑, Hepatoprotective Activity
*neuroP↑, Nephroprotective Activity
*P450↑, RA also reduced CP-produced oxidative stress and amplified cytochrome P450 2E1 (CYP2E1), HO-1, and renal-4-hydroxynonenal expression.
*HO-1↑,
*AntiAge↑, Anti-Aging Activity
*motorD↓, A significantly delays motor neuron dysfunction in paw grip endurance tests,

3030-

RosA,

Anticancer Activity of Rosmarinus officinalis L.: Mechanisms of Action and Therapeutic Potentials

Review,

Var,

ROS⇅, could defend against their oxidative damage of DNA, proteins, and lipids [15], although, as subsequently observed, the derivatives of rosemary are, in some conditions, capable of inducing a cytotoxic effect precisely through the release of ROS
*NRF2↑, scavenging action, RE has also been stated to control intracellular antioxidant systems, by stimulating the activation of nuclear transcription factor (Nrf)2 target genes
*GSH↑, augmenting the glutathione level, with an increase in its reduced form (GSH) compared with that of its oxidized form (GSSG)
HDAC2↓, Similar to the effects of SAHA, RA reduced cell growth and blocked cancer spheroid formation, caused the apoptosis of tumor cells, and blocked the expression of HDAC2

3029-

RosA,

Rosmarinic Acid, a Component of Rosemary Tea, Induced the Cell Cycle Arrest and Apoptosis through Modulation of HDAC2 Expression in Prostate Cancer Cell Lines

in-vitro,

Pca,

PC3

in-vitro,

Pca,

DU145

TumCP↓, RA decreased the cell proliferation in cell viability assay, and inhibited the colony formation and tumor spheroid formation.
tumCV↓,
Apoptosis↑, RA induced early- and late-stage apoptosis of PC-3 and DU145 cells
HDAC2↓, RA inhibited the expression of HDAC2, as SAHA did
PCNA↓, (PCNA), cyclin D1 and cyclin E1 were downregulated by RA, whereas p21 was upregulated. In addition,
cycD1/CCND1↓,
cycE/CCNE↓,
P21↑,
DNAdam↑, apoptotic cells observed by DNA fragmentation were significantly increased
Casp3↑, expression of Caspase-3 was upregulated by SAHA and RA in both cell lines

4201-

SFN,

Activation of BDNF by transcription factor Nrf2 contributes to antidepressant-like actions in rodents

in-vivo,

NA,

mice

*NRF2↑, Activation of Nrf2 by sulforaphane (SFN) showed fast-acting antidepressant-like effects in mice by activating BDNF as well as by inhibiting the expression of its transcriptional repressors (HDAC2, mSin3A, and MeCP2)
*BDNF↑,
*HDAC2↓,
*Mood↑,

4198-

SFN,

Sulforaphane epigenetically enhances neuronal BDNF expression and TrkB signaling pathways

vitro+vivo,

AD,

Mouse primary cortical neurons and a triple-transgenic mouse model of Alzheimers disease  3 × Tg-AD

*TrkB↑, Sulforaphane elevated levels of synaptic TrkB signaling pathway components, including CREB, CaMKII, ERK, and Akt in both primary cortical neurons and 3 × Tg-AD mice.
*CREB↑,
CaMKII ↑,
*ERK↑,
*ac‑H3↑, Sulforaphane increased global acetylation of histone 3 (H3) and H4, inhibited HDAC activity, and decreased the level of HDAC2 in primary cortical neurons
*ac‑H4↑,
*HDAC↓,
*HDAC2↓,
*BDNF↑, sulforaphane increased acetylated H3 and H4 at BDNF promoters, suggesting that sulforaphane regulates BDNF expression via HDAC inhibition.

3661-

SFN,

Beneficial Effects of Sulforaphane Treatment in Alzheimer's Disease May Be Mediated through Reduced HDAC1/3 and Increased P75NTR Expression

in-vitro,

AD,

mice

*cognitive↑, sulforaphane ameliorated behavioral cognitive impairments and attenuated brain Aβ burden in Alzheimer's disease model mice.
*HDAC1↓, sulforaphane reduced the expression of histone deacetylase1, 2, and 3,
*HDAC2↓,
*HDAC3↓,
*H3↑, increased levels of acetylated histone 3 lysine 9 and acetylated histone 4 lysine 12 in the cerebral cortex of Alzheimer's disease model mice
*H4↑,
*Aβ↓, reduce the Aβ burden in Alzheimer's disease model mice
*BioAv↑, Orally administered SFN is absorbed rapidly, resulting in high absolute bioavailability and crosses the blood-brain barrier readily
*BBB↑,
*neuroP↑, SFN may have a protective effect for cognitive function and neurons through reducing Aβ deposition and/or against Aβ toxicity.

1437-

SFN,

Dietary Sulforaphane in Cancer Chemoprevention: The Role of Epigenetic Regulation and HDAC Inhibition

Review,

NA,

HDAC↓, 15 μM
HDAC1↓,
HDAC2↓,
HDAC3↓,
HDAC8↓,
eff↑, this evidence suggests that sulforaphane may also compromise DNA repair mechanisms in cancer cells with selectivity.
ac‑HSP90↑,
DNMT1↓, 10 μM sulforaphane in 6 days inhibited DNMT1 and DNMT3a expression by 48% and 78%, respectively
DNMT3A↓,
hTERT/TERT↓,
NRF2↑, enhance nuclear translocation of Nrf2 and increase expression of Nrf2-target antioxidant genes, including HO-1, NQO1, and UGT1A1
HO-1↑,
NQO1↑,
miR-155↓,
miR-200c↑,
SOX9↓,
*toxicity↓, broccoli sprout-infused beverage containing 400 μM glucoraphanin nightly for 2 weeks causing no adverse effects and being well tolerated in 200 subjects

3322-

SIL,

Therapeutic intervention of silymarin on the migration of non-small cell lung cancer cells is associated with the axis of multiple molecular targets including class 1 HDACs, ZEB1 expression, and restoration of miR-203 and E-cadherin expression

in-vitro,

Lung,

A549

0, 5, 10 and 20 µg/mL) for 24 h

in-vitro,

Lung,

H1299

in-vitro,

Lung,

H460

HDAC↓, associated with the inhibition of histone deacetylase (HDAC) activity and reduced levels of class 1 HDAC proteins (HDAC1, HDAC2, HDAC3 and HDAC8
HDAC1↓,
HDAC2↓,
HDAC3↓,
HDAC8↓,
HATs↑, and concomitant increases in the levels of histone acetyltransferase activity (HAT).
Zeb1↓, Treatment of A549 and H460 cells with silymarin reduced the expression of the transcription factor ZEB1 and restored expression of E-cadherin.
E-cadherin↑,
TumCMig↓, These findings indicate that silymarin can effectively inhibit lung cancer cell migration

2105-

TQ,

Thymoquinone Promotes Pancreatic Cancer Cell Death and Reduction of Tumor Size through Combined Inhibition of Histone Deacetylation and Induction of Histone Acetylation

in-vitro,

PC,

AsPC-1

10–50 μM

in-vitro,

PC,

MIA PaCa-2

in-vitro,

PC,

Hs766t

in-vivo,

NA,

mice

tumCV↓, Tq (10–50 μM) inhibited cell viability and proliferation and caused partial G2 cycle arrest in dose-dependent manner in both cell lines.
TumCP↓,
TumCCA↑, Cells accumulated in subG0/G1 phase, indicating apoptosis
Apoptosis↑,
P53↑, upregulation of p53 and downregulation of Bcl-2.
Bcl-2↓,
P21↑, Tq increased p21 mRNA expression 12-fold
ac‑H4↑, Tq also induced H4 acetylation
HDAC↓, downregulated HDACs activity, reducing expression of HDACs 1, 2, and 3 by 40–60%
HDAC1↓,
HDAC2↓,
HDAC3↓,
TumVol↓, Tq significantly reduced tumor size in 67% of established tumor xenografts

3422-

TQ,

Thymoquinone, as a Novel Therapeutic Candidate of Cancers

Review,

Var,

selectivity↑, TQ selectively inhibits the cancer cells’ proliferation in leukemia [9], breast [10], lungs [11], larynx [12], colon [13,14], and osteosarcoma [15]. However, there is no effect against healthy cells
P53↑, It also re-expressed tumor suppressor genes (TSG), such as p53 and Phosphatase and tensin homolog (PTEN) in lung cancer
PTEN↑,
NF-kB↓, antitumor properties by regulating different targets, such as nuclear factor kappa B (NF-Kb), peroxisome proliferator-activated receptor-γ (PPARγ), and c-Myc [1], which resulted in caspases protein activation
PPARγ↓,
cMyc↓,
Casp↑,
*BioAv↓, Due to hydrophobicity, there are limitations in the bioavailability and drug formation of TQ.
BioAv↝, TQ is sensitive to light; a short period of exposure results in severe degradation, regardless of the solution’s acidity and solvent type [27]. It is also unstable in alkaline solutions because TQ’s stability decreases with rising pH
eff↑, Encapsulating TQ with CS improves the uptake and bioavailability of TQ but has low encapsulation efficiency (35%)
survivin↓, TQ showed antiproliferative and pro-apoptotic potency on breast cancer through the suppression of anti-apoptotic proteins, such as survivin, Bcl-xL, and Bcl-2
Bcl-xL↓,
Bcl-2↓,
Akt↓, treating doxorubicin-resistant MCF-7/DOX cells with TQ inhibited Akt and Bcl2 phosphorylation and increased the expression of PTEN and apoptotic regulators such as Bax, cleaved PARP, cleaved caspases, p53, and p21 [
BAX↑,
cl‑PARP↑,
CXCR4↓, inhibited metastasis with significant inhibition of chemokine receptor Type 4 (CXCR4), which is considered a poor prognosis indicator, matrix metallopeptidase 9 (MMP9), vascular endothelial growth factor Receptor 2 (VEGFR2), Ki67, and COX2
MMP9↓,
VEGFR2↓,
Ki-67↓,
COX2↓,
JAK2↓, TQ at 25, 50 and 75 µM inhibited JAK2 and c-Src activity and induced apoptosis by inhibiting the phosphorylation of STAT3 and STAT3 downstream genes, such as Bcl-2, cyclin D, survivin, and VEGF, and upregulating caspases-3, caspases-7, and caspases-9
cSrc↓,
Apoptosis↑,
p‑STAT3↓,
cycD1/CCND1↓,
Casp3↑,
Casp7↑,
Casp9↑,
N-cadherin↓, downregulated the mesenchymal genes expression N-cadherin, vimentin, and TWIST, while upregulating epithelial genes like E-cadherin and cytokeratin-19.
Vim↓,
Twist↓,
E-cadherin↑,
ChemoSen↑, The combined treatment of 5 μM TQ and 2 μg/mL cisplatin was more effective in cancer growth and progression than either agent alone in a xenograft tumor mouse model.
eff↑, TQ–artemisinin hybrid therapy (2.6 μM) showed an enhanced ROS generation level and concomitant DNA damage induction in human colon cancer cells, while not affecting nonmalignant colon epithelial at 100 μM
EMT↓, TQ inhibits the survival signaling pathways to reduce carcinogenesis progress rate, and decreases cancer metastasis through regulation of epithelial to mesenchymal transition (EMT).
ROS↑, Apoptosis is induced by TQ in cancer cells through producing ROS, demethylating and re-expressing the TSG
DNMT1↓, inhibits DNMT1, figure 2
eff↑, TQ–vitamin D3 combination significantly reduced pro-cancerous molecules (Wnt, β-catenin, NF-κB, COX-2, iNOS, VEGF and HSP-90) a
EZH2↓, reduced angiogenesis by downregulating significant angiogenic genes such as versican (VCAN), the growth factor receptor-binding protein 2 (Grb2), and enhancer of zeste homolog 2 (EZH2), which participates in histone methylatio
hepatoP↑, Moreover, TQ improved liver function as well as reduced hepatocellular carcinoma progression
Zeb1↓, TQ decreases the Twist1 and Zeb1 promoter activities,
RadioS↑, TQ combined with radiation inhibited proliferation and induced apoptosis more than a TQ–cisplatin combination against SCC25 and CAL27 cell lines
HDAC↓, TQ has inhibited the histone deacetylase (HDAC) enzyme and reduced its total activity.
HDAC1↓, as well as decreasing the expression of HDAC1, HDAC2, and HDAC3 by 40–60%
HDAC2↓,
HDAC3↓,
*NAD↑, In non-cancer cells, TQ can increase cellular NAD+
*SIRT1↑, An increase in the levels of intracellular NAD+ led to the activation of the SIRT1-dependent metabolic pathways
SIRT1↓, On the other hand, TQ induced apoptosis by downregulating SIRT1 and upregulating p73 in the T cell leukemia Jurkat cell line
*Inflam↓, TQ treatment of male Sprague–Dawley rats has reduced the inflammatory markers (CRP, TNF-α, IL-6, and IL-1β) and anti-inflammatory cytokines (IL-10 and IL-4) triggered by sodium nitrite
*CRP↓,
*TNF-α↓,
*IL6↓,
*IL1β↓,
*eff↑, The TQ–piperin combination has also decreased the oxidative damage triggered by microcystin in liver tissue and reduced malondialdehyde (MDA) and NO, while inducing glutathione (GSH) levels and superoxide dismutase (SOD), catalase (CAT), and glutathi
*MDA↓,
*NO↓,
*GSH↑,
*SOD↑,
*Catalase↑,
*GPx↑,
PI3K↓, repressing the activation of vital pathways, such as JAK/STAT and PI3K/AKT/mTOR.
mTOR↓,

Showing Research Papers: 1 to 21 of 21

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 21

Pathway results for Effect on Cancer / Diseased Cells:

Functional Outcomes ⓘ

AntiCan↑, 1, hepatoP↑, 1, TumVol↓, 2,
Total Targets: 154

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

antiOx↑, 3, Catalase↑, 4, GPx↑, 2, GSH↑, 4, GSTs↑, 1, HO-1↑, 1, Iron↓, 1, lipid-P↓, 1, MDA↓, 2, NRF2↑, 5, ROS↓, 5, SOD↑, 4, VitC↑, 1, VitE↑, 1,

Metal & Cofactor Biology ⓘ

IronCh↑, 1,

Mitochondria & Bioenergetics ⓘ

MMP↓, 1, MMP↑, 1,

Core Metabolism/Glycolysis ⓘ

CREB↑, 1, NAD↑, 1, SIRT1↑, 1,

Cell Death ⓘ

p‑JNK↓, 1, p38↓, 1,

Transcription & Epigenetics ⓘ

H3↑, 1, ac‑H3↑, 1, H4↑, 1, ac‑H4↑, 1, other↓, 1,

Proliferation, Differentiation & Cell State ⓘ

ERK↑, 1, HDAC↓, 1, HDAC1↓, 1, HDAC2↓, 4, HDAC3↓, 1, p‑mTOR↓, 1,

Angiogenesis & Vasculature ⓘ

NO↓, 1,

Barriers & Transport ⓘ

BBB↑, 1,

Immune & Inflammatory Signaling ⓘ

COX2↓, 1, CRP↓, 1, HMGB1↓, 1, IL1β↓, 3, IL6↓, 3, Inflam↓, 4, NF-kB↓, 1, p‑NF-kB↓, 1, PGE2↓, 1, TNF-α↓, 2,

Synaptic & Neurotransmission ⓘ

BDNF↑, 3, p‑tau↓, 1, TrkB↑, 1,

Protein Aggregation ⓘ

Aβ↓, 2,

Drug Metabolism & Resistance ⓘ

BioAv↓, 1, BioAv↑, 1, BioAv↝, 1, eff↑, 1, P450↑, 1,

Clinical Biomarkers ⓘ

BG↓, 1, CRP↓, 1, GutMicro↑, 1, IL6↓, 3,

Functional Outcomes ⓘ

AntiAge↑, 2, cardioP↑, 2, CardioT↓, 1, chemoP↑, 1, cognitive↑, 2, hepatoP↑, 1, memory↑, 1, Mood↑, 1, motorD↓, 1, neuroP↑, 4, toxicity↓, 1,
Total Targets: 69

Scientific Paper Hit Count for: HDAC2, Histone Deacetylase 2

5 Sulforaphane (mainly Broccoli)
5 Rosmarinic acid
2 Thymoquinone
1 Butyrate
1 EGCG (Epigallocatechin Gallate)
1 Emodin
1 Gallic acid
1 Genistein (soy isoflavone)
1 Luteolin
1 Oleuropein
1 HydroxyTyrosol
1 Propolis -bee glue
1 Quercetin
1 Silymarin (Milk Thistle) silibinin

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

Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:%  Target#:984  State#:%  Dir#:1
  wNotes=on  sortOrder:rid,rpid

HDAC2 Cancer Research Results

Pathway results for Effect on Cancer / Diseased Cells:

Redox & Oxidative Stress ⓘ

Mitochondria & Bioenergetics ⓘ

Core Metabolism/Glycolysis ⓘ

Cell Death ⓘ

Kinase & Signal Transduction ⓘ

Transcription & Epigenetics ⓘ

Protein Folding & ER Stress ⓘ

Autophagy & Lysosomes ⓘ

DNA Damage & Repair ⓘ

Cell Cycle & Senescence ⓘ

Proliferation, Differentiation & Cell State ⓘ

Migration ⓘ

Angiogenesis & Vasculature ⓘ

Barriers & Transport ⓘ

Immune & Inflammatory Signaling ⓘ

Protein Aggregation ⓘ

Drug Metabolism & Resistance ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

Metal & Cofactor Biology ⓘ

Mitochondria & Bioenergetics ⓘ

Core Metabolism/Glycolysis ⓘ

Cell Death ⓘ

Transcription & Epigenetics ⓘ

Proliferation, Differentiation & Cell State ⓘ

Angiogenesis & Vasculature ⓘ

Barriers & Transport ⓘ

Immune & Inflammatory Signaling ⓘ

Synaptic & Neurotransmission ⓘ

Protein Aggregation ⓘ

Drug Metabolism & Resistance ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

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