HDAC3 Cancer Research Results

HDAC3, Histone Deacetylase 3: Click to Expand ⟱

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Type:

HDAC3 is an enzyme belonging to the class I histone deacetylases and plays a key role in transcriptional regulation by removing acetyl groups from histone tails.
This deacetylase activity leads to chromatin condensation and generally results in transcriptional repression.
HDAC3 is involved in multiple cellular processes, including cell cycle regulation, apoptosis, and differentiation.

HDAC3 is frequently found to be overexpressed in several cancer types, including breast, colorectal, liver, lung, and hematological malignancies.
Elevated HDAC3 levels have been associated with the repression of tumor suppressor genes and deregulation of proliferative pathways.

Scientific Papers found: Click to Expand⟱

1151-

Api,

Plant flavone apigenin inhibits HDAC and remodels chromatin to induce growth arrest and apoptosis in human prostate cancer cells: In vitro and in vivo study

in-vitro,

Pca,

PC3

20–40μM

in-vitro,

Pca,

22Rv1

in-vivo,

NA,

oral intake of apigenin at doses of 20 and 50μg/mouse/day

mouse

TumCCA↑,
Apoptosis↑,
HDAC↓, HDAC1 and HDAC3
P21↑,
BAX↑,
TumCG↓,
Bcl-2↓,
Bax:Bcl2↑, shifting the bax/bcl2 ratio in favor of apoptosis
HDAC1↓,
HDAC3↓,

2639-

Api,

Plant flavone apigenin: An emerging anticancer agent

Review,

Var,

*antiOx↑, Apigenin (4′, 5, 7-trihydroxyflavone), a major plant flavone, possessing antioxidant, anti-inflammatory, and anticancer properties
*Inflam↓,
AntiCan↑,
ChemoSen↑, Studies demonstrate that apigenin retain potent therapeutic properties alone and/or increases the efficacy of several chemotherapeutic drugs in combination on a variety of human cancers.
BioEnh↑, Apigenin’s anticancer effects could also be due to its differential effects in causing minimal toxicity to normal cells with delayed plasma clearance and slow decomposition in liver increasing the systemic bioavailability in pharmacokinetic studies.
chemoPv↑, apigenin highlighting its potential activity as a chemopreventive and therapeutic agent.
IL6↓, In taxol-resistant ovarian cancer cells, apigenin caused down regulation of TAM family of tyrosine kinase receptors and also caused inhibition of IL-6/STAT3 axis, thereby attenuating proliferation.
STAT3↓,
NF-kB↓, apigenin treatment effectively inhibited NF-κB activation, scavenged free radicals, and stimulated MUC-2 secretion
IL8↓, interleukin (IL)-6, and IL-8
eff↝, The anti-proliferative effects of apigenin was significantly higher in breast cancer cells over-expressing HER2/neu but was much less efficacious in restricting the growth of cell lines expressing HER2/neu at basal levels
Akt↓, Apigenin interferes in the cell survival pathway by inhibiting Akt function by directly blocking PI3K activity
PI3K↓,
HER2/EBBR2↓, apigenin administration led to the depletion of HER2/neu protein in vivo
cycD1/CCND1↓, Apigenin treatment in breast cancer cells also results in decreased expression of cyclin D1, D3, and cdk4 and increased quantities of p27 protein
CycD3↓,
p27↑,
FOXO3↑, In triple-negative breast cancer cells, apigenin induces apoptosis by inhibiting the PI3K/Akt pathway thereby increasing FOXO3a expression
STAT3↓, In addition, apigenin also down-regulated STAT3 target genes MMP-2, MMP-9, VEGF and Twist1, which are involved in cell migration and invasion of breast cancer cells [
MMP2↓,
MMP9↓,
VEGF↓, Apigenin acts on the HIF-1 binding site, which decreases HIF-1α, but not the HIF-1β subunit, thereby inhibiting VEGF.
Twist↓,
MMP↓, Apigenin treatment of HGC-27 and SGC-7901 gastric cancer cells resulted in the inhibition of proliferation followed by mitochondrial depolarization resulting in apoptosis
ROS↑, Further studies revealed apigenin-induced apoptosis in hepatoma tumor cells by utilizing ROS generated through the activation of the NADPH oxidase
NADPH↑,
NRF2↓, Apigenin significantly sensitized doxorubicin-resistant BEL-7402 (BEL-7402/ADM) cells to doxorubicin (ADM) and increased the intracellular concentration of ADM by reducing Nrf2-
SOD↓, In human cervical epithelial carcinoma HeLa cells combination of apigenin and paclitaxel significantly increased inhibition of cell proliferation, suppressing the activity of SOD, inducing ROS accumulation leading to apoptosis by activation of caspas
COX2↓, melanoma skin cancer model where apigenin inhibited COX-2 that promotes proliferation and tumorigenesis
p38↑, Additionally, it was shown that apigenin treatment in a late phase involves the activation of p38 and PKCδ to modulate Hsp27, thus leading to apoptosis
Telomerase↓, apigenin inhibits cell growth and diminishes telomerase activity in human-derived leukemia cells
HDAC↓, demonstrated the role of apigenin as a histone deacetylase inhibitor. As such, apigenin acts on HDAC1 and HDAC3
HDAC1↓,
HDAC3↓,
Hif1a↓, Apigenin acts on the HIF-1 binding site, which decreases HIF-1α, but not the HIF-1β subunit, thereby inhibiting VEGF.
angioG↓, Moreover, apigenin was found to inhibit angiogenesis, as suggested by decreased HIF-1α and VEGF expression in cancer cells
uPA↓, Furthermore, apigenin intake resulted in marked inhibition of p-Akt, p-ERK1/2, VEGF, uPA, MMP-2 and MMP-9, corresponding with tumor growth and metastasis inhibition in TRAMP mice
Ca+2↑, Neuroblastoma SH-SY5Y cells treated with apigenin led to induction of apoptosis, accompanied by higher levels of intracellular free [Ca(2+)] and shift in Bax:Bcl-2 ratio in favor of apoptosis, cytochrome c release, followed by activation casp-9, 12
Bax:Bcl2↑,
Cyt‑c↑,
Casp9↑,
Casp12↑,
Casp3↑, Apigenin also augmented caspase-3 activity and PARP cleavage
cl‑PARP↑,
E-cadherin↑, Apigenin treatment resulted in higher levels of E-cadherin and reduced levels of nuclear β-catenin, c-Myc, and cyclin D1 in the prostates of TRAMP mice.
β-catenin/ZEB1↓,
cMyc↓,
CDK4↓, apigenin exposure led to decreased levels of cell cycle regulatory proteins including cyclin D1, D2 and E and their regulatory partners CDK2, 4, and 6
CDK2↓,
CDK6↓,
IGF-1↓, A reduction in the IGF-1 and increase in IGFBP-3 levels in the serum and the dorsolateral prostate was observed in apigenin-treated mice.
CK2↓, benefits of apigenin as a CK2 inhibitor in the treatment of human cervical cancer by targeting cancer stem cells
CSCs↓,
FAK↓, Apigenin inhibited the tobacco-derived carcinogen-mediated cell proliferation and migration involving the β-AR and its downstream signals FAK and ERK activation
Gli↓, Apigenin inhibited the self-renewal capacity of SKOV3 sphere-forming cells (SFC) by downregulating Gli1 regulated by CK2α
GLUT1↓, Apigenin induces apoptosis and slows cell growth through metabolic and oxidative stress as a consequence of the down-regulation of glucose transporter 1 (GLUT1).

1505-

CUR,

Epigenetic targets of bioactive dietary components for cancer prevention and therapy

Review,

NA,

25 μM @24hr

TumCCA↑,
Apoptosis↑,
DNMTs↓, curcumin also inhibits DNMT activities and histone modification such as HDAC inhibition in tumorigenesis
HDAC↓,
HATs↓, inhibitory activity against HDACs and HATs in several in vitro cancer models
TumCP↓,
p300↓, Significant decreases in the amounts of p300, HDAC1, HDAC3, and HDAC8
HDAC1↓,
HDAC3↓,
HDAC8↓,
NF-kB↓, inhibition of nuclear translocation of the NF-κB/p65 subunit

3709-

dietSTF,

Intermittent Fasting Protects against Alzheimer’s Disease Possible through Restoring Aquaporin-4 Polarity

in-vitro,

AD,

 mouse model of AD

*cognitive↑, results showed that IF ameliorated cognitive dysfunction, prevented brain from Aβ deposition, and restored the AQP4 polarity in a mouse model of AD
*Aβ↓,
*AQPs↓, IF down-regulated the expression of AQP4-M1 and histone deacetylase 3, reduced AQP4-M1/M23 ratio,
*HDAC3↓,

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↑,

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↓,

2877-

HNK,

Targeting histone deacetylase-3 blocked epithelial-mesenchymal plasticity and metastatic dissemination in gastric cancer

in-vitro,

GC,

AGS

HDAC3↓, Honokiol significantly abolished HDAC3 activity (Y298) via inhibition of NFκBp65/CEBPβ signaling,
NF-kB↓,
CEBPB↓,
ER Stress↑, Honokiol increased ER stress markers and inhibited EMT-associated epithelial markers, but decreased Wnt/β-catenin activity
EMT↓,
Wnt↓,
β-catenin/ZEB1↓,

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

1506-

RES,

Epigenetic targets of bioactive dietary components for cancer prevention and therapy

Review,

NA,

DNMTs↓, weaker DNMT inhibitory activity than other dietary bioactive components such as EGCG
BRCA1↑, resveratrol treatment, which was associated with BRAC-1 reactivation in MCF-7 cells
HDAC↓, resveratrol is associated with activation of the type III HDAC inhibitors, sirtuin 1 (SIRT1), and p300, in multiple in vitro and in vivo models
SIRT1↑,
p300↓, Significant decreases in the amounts of p300, HDAC1, HDAC3, and HDAC8
survivin↓,
HDAC1↓,
HDAC3↓,
HDAC8↓,

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.

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↓,

1730-

SFN,

Sulforaphane: An emergent anti-cancer stem cell agent

Review,

Var,

BioAv↓, When exposed to high temperatures during meal preparation, myrosinase can be degraded, lose its function, and subsequently compromise the synthesis of SFN.
BioAv↑, eating raw cruciferous vegetables, instead of heating them can significantly improve the biodisponibility of SFN and its subsequent beneficial effects.
GSTA1↑, induction of Phase II enzymes [glutathione S-transferase (GST)
P450↓, (cytochrome P450, CYP) inhibition
TumCCA↑, herb-derived agent can also promote cell cycle arrest and apoptosis by regulating different signaling pathways including Nuclear Factor erythroid Related Factor 2 (Nrf2)-Keap1 and NF-κB.
HDAC↓, modulate the activity of some epigenetic factors, such as histone deacetylases (HDAC),
P21↑, upregulation of p21 and p27,
p27↑,
DNMT1↓, SFN was able to decrease the expression of DNMT1 and DNMT3 in LnCap prostate cancer cells
DNMT3A↓,
cycD1/CCND1↑, reduce methylation in Cyclin D2 promoter, thus inducing Cyclin D2 gene expression in those cells
DNAdam↑, SFN induced DNA damage, enhanced Bax expression and the release of cytochrome C followed by apoptosis
BAX↑,
Cyt‑c↑,
Apoptosis↑,
ROS↑, SFN increased reactive oxygen species (ROS), apoptosis-inducing factor (AIF)
AIF↑,
CDK1↑,
Casp3↑, activation of caspase-3, -8, and -9
Casp8↑,
Casp9↑,
NRF2↑, SFN significantly activated the major antioxidant marker Nrf2 and decreased NFκB, TNF-α, IL-1β
NF-kB↓,
TNF-α↓,
IL1β↓,
CSCs↓, SFN, have attracted attention due to their anti-CSC effect
CD133↓,
CD44↓,
ALDH↓,
Nanog↓,
OCT4↓,
hTERT/TERT↓,
MMP2↓,
EMT↓, SFN was reported to inhibit EMT and metastasis in the NSCLC, the cell lines H1299
ALDH1A1↓, ALDH1A1), Wnt3, and Notch4, other CSC-related genes inhibited by SFN treatment
Wnt↓,
NOTCH↓, SFN can inhibit aberrantly activated embryonic pathways in CSCs, including Sonic Hedgehog (SHH), Wnt/β-catenin, Cripto-1 (CR-1), and Notch.
ChemoSen↑, These results suggest that the antioxidant properties of SFN do not impact the cytotoxicity of antineoplastic drugs, but on the contrary, seems to improve it.
*Ki-67↓, Ki-67 and HDAC3 levels significantly decreased in benign breast tissues, and there was also a reduction in HDAC activity in blood cells
*HDAC3↓,
*HDAC↓,

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

1430-

SFN,

Sulforaphane bioavailability and chemopreventive activity in women scheduled for breast biopsy

Trial,

BC,

250 μM GFN glucoraphanin

*HDAC3↓, HDAC3 (p = 0.044) levels significantly decreased in benign tissue
HDAC↓,
*toxicity↓, GFN supplementation for a few weeks is safe but may not be sufficient for producing changes in breast tissue tumor biomarkers.

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 17 of 17

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 17

Pathway results for Effect on Cancer / Diseased Cells:

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

antiOx↑, 1, Catalase↑, 2, GPx↑, 1, GSH↑, 2, MDA↓, 2, NRF2↑, 1, ROS↓, 1, SOD↑, 2,

Core Metabolism/Glycolysis ⓘ

NAD↑, 1, SIRT1↑, 1,

Transcription & Epigenetics ⓘ

H3↑, 1, H4↑, 1,

Proliferation, Differentiation & Cell State ⓘ

HDAC↓, 1, HDAC1↓, 1, HDAC2↓, 1, HDAC3↓, 4,

Migration ⓘ

Ki-67↓, 1,

Angiogenesis & Vasculature ⓘ

NO↓, 1,

Barriers & Transport ⓘ

AQPs↓, 1, BBB↑, 1,

Immune & Inflammatory Signaling ⓘ

CRP↓, 1, IL1β↓, 1, IL6↓, 1, Inflam↓, 3, TNF-α↓, 1,

Protein Aggregation ⓘ

Aβ↓, 2,

Drug Metabolism & Resistance ⓘ

BioAv↓, 1, BioAv↑, 1, eff↑, 1,

Clinical Biomarkers ⓘ

CRP↓, 1, IL6↓, 1, Ki-67↓, 1,

Functional Outcomes ⓘ

chemoP↑, 1, cognitive↑, 2, neuroP↑, 1, toxicity↓, 2,
Total Targets: 36

Scientific Paper Hit Count for: HDAC3, Histone Deacetylase 3

6 Sulforaphane (mainly Broccoli)
2 Apigenin (mainly Parsley)
2 Thymoquinone
1 Curcumin
1 diet Short Term Fasting
1 EGCG (Epigallocatechin Gallate)
1 Genistein (soy isoflavone)
1 Honokiol
1 Oleuropein
1 HydroxyTyrosol
1 Resveratrol
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#:1023  State#:%  Dir#:1
  wNotes=on  sortOrder:rid,rpid

HDAC3 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 ⓘ

Hormonal & Nuclear Receptors ⓘ

Drug Metabolism & Resistance ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

Core Metabolism/Glycolysis ⓘ

Transcription & Epigenetics ⓘ

Proliferation, Differentiation & Cell State ⓘ

Migration ⓘ

Angiogenesis & Vasculature ⓘ

Barriers & Transport ⓘ

Immune & Inflammatory Signaling ⓘ

Protein Aggregation ⓘ

Drug Metabolism & Resistance ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

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