DNMT1 Cancer Research Results

DNMT1, DNA (cytosine-5-)-methyltransferase 1: Click to Expand ⟱

Source: CGL-Driver Genes

Type: Oncogene

DNMT1 overexpression in various cancer types.
DNA (cytosine-5-)-methyltransferase 1, commonly referred to as DNMT1, is an enzyme that plays a crucial role in the maintenance of DNA methylation patterns.
Increased DNMT1 activity can promote tumorigenesis by facilitating the accumulation of methylation changes that drive cancer progression.
Is frequently overexpressed in a variety of cancers, including breast, colorectal, lung, prostate, and hematological malignancies. This overexpression is often associated with hypermethylation of tumor suppressor genes, leading to their silencing and contributing to tumorigenesis.

Scientific Papers found: Click to Expand⟱

2665-

AL,

Anticancerous and Antimicrobial Properties of Garlic

Review,

Var,

DNMTs↓, A garlic derivative, S-Allylcysteine (SAC). SAC decreases global DNA methylation and also the levels of 5-methylcytosine, DNMT activity, messenger RNA (mRNA) and protein levels of DNMT1
DNMT1↓,

3435-

aLinA,

Alpha-linolenic acid-mediated epigenetic reprogramming of cervical cancer cell lines

in-vitro,

Cerv,

HeLa

in-vitro,

Cerv,

SiHa

in-vitro,

Cerv,

C33A

DNMTs↓, ALA increased DNA demethylase, HMTs, and HATs while decreasing global DNA methylation, DNMT, HDMs, and HDACs mRNA expression/activity in all cervical cancer cell lines.
HDAC↓,
HATs↑,
hTERT/TERT↓, ALA downregulated hTERT oncogene while upregulating the mRNA expression of TSGs (Tumor Suppressor Genes) CDH1, RARβ, and DAPK in all the cell lines.
CDH1↑,
RARβ↑,
DNMT1↓, In HeLa, ALA treatment reduced DNMT1 mRNA expression by 2.3-fold, 2.9-fold, and 3.3-fold at 20, 40, and 80 μM, respectively,
DNMT3A↓, ALA also reduced DNMT3B mRNA expression: in HeLa by 3.5-fold and 3.2-fold at 40 and 80 μM, i
TET2↑, ALA treatment induced TET2 mRNA expression, with an increase of 3.6-fold in HeLa at 80 μM.
HDAC1↓, ALA treatment in HeLa resulted in a significant reduction in HDAC1 mRNA expression, with decreases of 2.3-fold and 3.8-fold at 40 and 80 μM,
HDAC8↓, Treatment with ALA at 80 μM also led to reductions in HDAC8 mRNA expression by 2.4-fold, 2.0-fold, and 2.0-fold in HeLa, SiHa, and C33A, respectively.
SIRT1↓, ALA additionally decreased SIRT1 mRNA expression in HeLa by 2.4-fold and 2.5-fold at 40 and 80 μM, respectively.
HMTs↑,
EZH2↓, In HeLa, ALA treatment decreased EZH2 mRNA expression by 2.9-fold, 4.2-fold, and 4.2-fold at 20, 40, and 80 µM, respectively.

1561-

Api,

Apigenin Reactivates Nrf2 Anti-oxidative Stress Signaling in Mouse Skin Epidermal JB6 P + Cells Through Epigenetics Modifications

in-vivo,

Nor,

JB6

*NRF2↑, API enhanced the nuclear translocation of Nrf2
*DNMT1↓, API reduced the expression of the DNMT1, DNMT3a, and DNMT3b epigenetic proteins as well as the expression of some HDACs (1–8).
*DNMT3A↓,
*HDAC↓,
*AntiCan↑, results may provide new therapeutic insights into the prevention of skin cancer by dietary phytochemicals.

1433-

Ash,

SFN,

A Novel Combination of Withaferin A and Sulforaphane Inhibits Epigenetic Machinery, Cellular Viability and Induces Apoptosis of Breast Cancer Cells

in-vitro,

BC,

MCF-7

1.0 µM WA and 5.0 µM SFN

in-vitro,

BC,

MDA-MB-231

eff↑, synergistic inhibition of cellular viability in MCF-7
Bcl-2↓,
BAX↑,
tumCV↓,
DNMT1↓,
DNMT3A↓, DNMT3A and DNMT3B mRNA expression is down-regulated
HDAC↓, significant decreases in HDAC activity

2021-

BBR,

Berberine: An Important Emphasis on Its Anticancer Effects through Modulation of Various Cell Signaling Pathways

Review,

NA,

*antiOx?, Berberine has been noted as a potential therapeutic candidate for liver fibrosis due to its antioxidant and anti-inflammatory activities
*Inflam↓,
Apoptosis↑, Apoptosis induced by berberine in liver cancer cells caused cell cycle arrest at the M/G1 phase and increased the Bax expression
TumCCA↑,
BAX↑,
eff↑, mixture of curcumin and berberine effectively decreases growth in breast cancer cell lines
VEGF↓, berberine also prevented the expression of VEGF
PI3K↓, berberine plays an important role in cancer management through inhibition of the PI3K/AKT/mTOR pathway
Akt↓,
mTOR↓,
Telomerase↓, Berberine decreased the telomerase activity and level of the colorectal cancer cell line,
β-catenin/ZEB1↓, berberine and its derivatives have the ability to inhibit β-catenin/Wnt signaling in tumorigenesis
Wnt↓,
EGFR↓, berberine treatment decreased cell proliferation and epidermal growth factor receptor expression levels in the xenograft model.
AP-1↓, Berberine efficiently targets both the host and the viral factors accountable for cervical cancer development via inhibition of activating protein-1
NF-kB↓, berberine inhibited lung cancer cell growth by concurrently targeting NF-κB/COX-2, PI3K/AKT, and cytochrome-c/caspase signaling pathways
COX2↑,
NRF2↓, Berberine suppresses the Nrf2 signaling-related protein expression in HepG2 and Huh7 cells,
RadioS↑, suggesting that berberine supports radiosensitivity through suppressing the Nrf2 signaling pathway in hepatocellular carcinoma cells
STAT3↓, regulating the JAK–STAT3 signaling pathway
ERK↓, berberine prevented the metastatic potential of melanoma cells via a reduction in ERK activity, and the protein levels of cyclooxygenase-2 by a berberine-caused AMPK activation
AR↓, Berberine reduced the androgen receptor transcriptional activity
ROS↑, In a study on renal cancer, berberine raised the levels of autophagy and reactive oxygen species in human renal tubular epithelial cells derived from the normal kidney HK-2 cell line, in addition to human cell lines ACHN and 786-O cell line.
eff↑, berberine showed a greater apoptotic effect than gemcitabine in cancer cells
selectivity↑, After berberine treatment, it was noticed that berberine showed privileged selectivity towards cancer cells as compared to normal ones.
selectivity↑, expression of caspase-1 and its downstream target Interleukin-1β (IL-1β) was higher in osteosarcoma cells as compared to normal cells
BioAv↓, several studies have been undertaken to overcome the difficulties of low absorption and poor bioavailability through nanotechnology-based strategies.
DNMT1↓, In human multiple melanoma cell U266, berberine can inhibit the expression of DNMT1 and DNMT3B, which leads to hypomethylation of TP53 by altering the DNA methylation level and the p53-dependent signal pathway
cMyc↓, Moreover, berberine suppresses SLC1A5, Na+ dependent transporter expression through preventing c-Myc

2701-

BBR,

Berberine Inhibits KLF4 Promoter Methylation and Ferroptosis to Ameliorate Diabetic Nephropathy in Mice

in-vivo,

Diabetic,

MICE

*Inflam↓, Berberine has various biological activities, including anti-inflammation, antioxidative stress, and antiferroptosis
*antiOx↑,
*Ferroptosis↓,
*RenoP↑, Berberine rescued kidney function and renal structure and prevented renal fibrosis in diabetic nephropathy mice.
*DNMT1↓, Berberine suppressed the expression of DNMT1 and DNMT2 and upregulated KLF4 expression by preventing KLF4 promoter methylation.
*DNMTs↓,
*KLF4↑,

2702-

BBR,

The enhancement of combination of berberine and metformin in inhibition of DNMT1 gene expression through interplay of SP1 and PDPK1

in-vitro,

Lung,

A549

in-vitro,

Lung,

H1975

TumCG↓, BBR inhibited growth of non-small cell lung cancer (NSCLC) cells through mitogen-activated protein kinase (MAPK)-mediated increase in forkhead box O3a (FOXO3a).
MAPK↓,
FOXO3↑,
TumCCA↑, BBR not only induced cell cycle arrest, but also reduced migration and invasion of NSCLC cells
TumCMig↓,
TumCI↓,
Sp1/3/4↓, BBR reduced 3-phosphoinositide-dependent protein kinase-1 (PDPK1) and transcription factor SP1 protein expressions.
PDK1↓, BBR reduced 3-phosphoinositide-dependent protein kinase-1
DNMT1↓, BBR inhibited DNA methyltransferase 1 (DNMT1) gene expression and overexpressed DNMT1 resisted BBR-inhibited cell growth
eff↑, Finally, metformin enhanced the effects of BBR both in vitro and in vivo.

2712-

BBR,

Suppression of colon cancer growth by berberine mediated by the intestinal microbiota and the suppression of DNA methyltransferases (DNMTs)

in-vitro,

Colon,

HT29

in-vivo,

NA,

TumCG↓, BBR reduced the growth of colon cancer cells to a certain extent in vitro and in vivo,
GutMicro↑, BBR significantly mediated the abundance, composition and metabolic functions of the intestinal microbial flora in mice with colon cancer
other↝, The effect of BBR on inflammatory cytokines, including IL-6, FGF, and PDGF, was not obvious
IL10↓, BBR significantly downregulated IL-10 levels (P < 0.05) and reduced c-Myc, DNMT1, and DNMT3B
cMyc↓,
DNMT1↓,
DNMTs↓,

5179-

BBR,

Regulation of Cell Signaling Pathways by Berberine in Different Cancers: Searching for Missing Pieces of an Incomplete Jig-Saw Puzzle for an Effective Cancer Therapy

Review,

Var,

AMPK↑, Berberine has been shown to potently induce AMP-activated protein kinase (AMPK) in cancer cells
Casp3↑, TRAIL and berberine significantly activated caspase-3 and cleavage of PARP in TRAIL-resistant MDA-MB-468 BCa cells
cl‑PARP↑,
Mcl-1↓, Berberine dose-dependently induced degradation of Mcl-1 and c-FLIP
cFLIP↓,
β-catenin/ZEB1↓, Berberine efficiently inhibited nuclear accumulation of β-catenin.
Wnt↓, berberine to inhibit the WNT pathway in different cancers
STAT3↓, Berberine reduced protein levels of STAT3
mTOR↓, berberine has anti-tumor effects, through inhibition of the mTOR-signaling pathway.
Hif1a↓, HIF-1α protein expression, a well-known transcription factor critical for dysregulated cancer cell glucose metabolism, was considerably inhibited in berberine-treated colon cancer cell
NF-kB↓, Berberine also interfered with the NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) pathway and effectively inhibited colon cancer progression
SIRT1↑, Berberine was shown to upregulate some histone deacetylases (HDAC) of class II, such as sirtuin SIRT1 (sirtuin 1),
DNMT1↓, Berberine induced a decrease in activity of two DNA methylases, DNMT1 (DNA (cytosine-5)-methyltransferase 1) and DNMT3,
DNMT3A↓,
miR-29b↓, Berberine supplementation led to the miR29-b suppression, increasing insulin-like growth factor-binding protein (IGFBP1) expression in the liver;
IGFBP1↑,
eff↑, Silver nanoparticles proved successful in delivering berberine to human tongue squamous carcinoma SCC-25 cells, blocking cell cycle and increasing Bax/Bcl-2 ratio
chemoPv↑, uncovered tremendous chemopreventive ability of berberine to modulate signaling pathways
BioAv↓, Although some issues remain to be solved, such as its poor water solubility/stability and low bioavailability

5839-

CAP,

Capsaicin: beyond TRPV1

Review,

Var,

TRPV1↑, Besides its classical effects through activating the Transient Receptor Potential Vanilloid type 1 (TRPV1), growing experimental evidence demonstrates that capsaicin has pleiotropic actions in a TRPV1-independent manner.
eff↑, cancer cell lines co-treated with capsaicin and a well-characterized Hsp90 inhibitor, 17-AAG, showed improved anti-tumor effects (32).
DNMT1↓, Capsaicin generates an inhibitory effect on DNMT1

6023-

CGA,

Pharmacological advances of the chlorogenic acids family: current insights and future research directions

Review,

AD,

Review,

Park,

Review,

IBD,

*Aβ↓, chlorogenic acid can reduce Aβ plaques in Alzheimer’s disease model mice by 37%, indicating its neuroprotective potential.
*neuroP↑,
*cardioP↑, Similarly, CGAs offer protection to the cardiovascular system, gastrointestinal tract, kidneys, and liver, while additionally preventing metabolic syndrome and displaying anticancer and antimicrobial capabilities.
*GastroP↑,
*RenoP↑,
*hepatoP↑,
*Obesity↓,
*Bacteria↓,
*BioAv↑, hydroxycinnamoyl-CoA quinate hydroxycinnamoyl transferase, HQT in tomatoes significantly enhances CGA accumulation without significantly altering the levels of other soluble phenolic botanical drugs.
*BioAv↑, Mechanistic studies have shown that dietary fats (such as soybean oil and coconut oil) can significantly enhance the permeability of CGA in the Caco-2 monolayer by increasing cell membrane fluidity
*BioAv↑, Following oral administration of CGA, the acidic environment in the stomach helps maintain the structural stability of CGA, with approximately one-third of the dose entering the blood system through passive diffusion in the small intestine, while the
*ROS↓, CGA pretreatment markedly diminished ROS caused by PD toxins
*GutMicro↑, CGA works with the gut microbiota and its metabolites to alleviate post-infectious irritable bowel syndrome (PI-IBS)
*IBI↑, CGA increases intestinal damage repair, decreases MCT-1 and TFF-3 expression, and suppresses NF-κB expression
*MCT1↓,
*NF-kB↓,
*DNMT1↓, Liver Cancer, DNMT1 protein expression↓

422-

CUR,

Curcumin induces re-expression of BRCA1 and suppression of γ synuclein by modulating DNA promoter methylation in breast cancer cell lines

in-vitro,

BC,

HCC-38

5 and 10 µM, 3 days

in-vitro,

BC,

T47D

BRCA1↑,
TET1↑,
DNMT3A↑, Curcumin downregulates the expression of DNMT1 and upregulates TET1 and DNMT3 in HCC-38 cells
DNMT1↓,
SNCG↓,
miR-29b↓, HCC-38 cells
miR-29b↑, upregulates miR-29b in T47D cells

443-

CUR,

Reduced Caudal Type Homeobox 2 (CDX2) Promoter Methylation Is Associated with Curcumin’s Suppressive Effects on Epithelial-Mesenchymal Transition in Colorectal Cancer Cells

in-vitro,

CRC,

SW480

DNMT1↓,
DNMT3A↓,
N-cadherin↓,
Vim↓,
Wnt↓, Wnt3a
Snail↓, Snail1
Twist↓,
β-catenin/ZEB1↓,
E-cadherin↑,
EMT↓, Curcumin incubation inhibited EMT
CDX2↓,

4671-

CUR,

Targeting colorectal cancer stem cells using curcumin and curcumin analogues: insights into the mechanism of the therapeutic efficacy

in-vitro,

CRC,

CSCs↓, Intriguingly, curcumin and its analogues have also recently been shown to be effective in lowering tumour recurrence by targeting the CSC population, hence inhibiting tumour growth.
TumCG↓,
ChemoSen↑, curcumin could play a role as chemosensitiser whereby the colorectal CSCs are now sensitised towards the anti-cancer therapy,
Wnt↓, Three major signaling pathways in which curcumin plays a pivotal role in CSC self-renewal behavior are the Wnt/β-catenin, Sonic Hedgehog (SHH), and Notch pathways
β-catenin/ZEB1↓,
Shh↓,
NOTCH↓,
DNMT1↓, Figure 1
STAT3↓,
NF-kB↓,
EGFR↓,
IGFR↓,
TumCCA↓,
cl‑PARP↑,
BAX↑,
ECM/TCF↓,

2688-

CUR,

Effects of resveratrol, curcumin, berberine and other nutraceuticals on aging, cancer development, cancer stem cells and microRNAs

Review,

Var,

Review,

AD,

*ROS↓, CUR reduced the production of ROS
*SOD↑, CUR also upregulated the expression of superoxide dismutase (SOD) genes
p16↑, The effects of CUR on gene expression in cancer-associated fibroblasts obtained from breast cancer patients has been examined. CUR increased the expression of the p16INK4A and other tumor suppressor proteins
JAK2↓, CUR decreased the activity of the JAK2/STAT3 pathway
STAT3↓,
CXCL12↓, and many molecules involved in cellular growth and metastasis including: stromal cell-derived factor-1 (SDF-1), IL-6, MMP2, MMP9 and TGF-beta
IL6↓,
MMP2↓,
MMP9↓,
TGF-β↓,
α-SMA↓, These effects reduced the levels of alpha-smooth muscle actin (alpha-SMA) which was attributed to decreased migration and invasion of the cells.
LAMs↓, CUR suppressed Lamin B1 and
DNAdam↑, induced DNA damage-independent senescence in proliferating but not quiescent breast stromal fibroblasts in a p16INK4A-dependent manner.
*memory↑, CUR has recently been shown to suppress memory decline by suppressing beta-site amyloid precursor protein cleaving enzyme 1 (BACE1= Beta-secretase 1, an important gene in AD) expression which is implicated in beta-amyoid pathology in 5xFAD transgenic
*cognitive↑, CUR was found to decrease adiposity and improve cognitive function in a similar fashion as CR in 15-month-old mice.
*Inflam↓, The effects of CUR and CR were positively linked with anti-inflammatory or antioxidant actions
*antiOx↑,
*NO↑, CUR treatment increased nNOS expression, acidity and NO concentration
*MDA↓, CUR treatment resulted in decreased levels of MDA
*ROS↓, CUR treatment was determined to cause reduction of ROS in the AMD-RPEs and protected the cells from H2O2-induced cell death by reduction of ROS levels.
DNMT1↓, CUR has been shown to downregulate the expression of DNA methyl transferase I (DNMT1)
ROS↑, induction of ROS and caspase-3-mediated apoptosis
Casp3↑,
Apoptosis↑,
miR-21↓, CUR was determined to decrease both miR-21 and anti-apoptotic protein expression.
LC3II↓, CUR also induced proteins associated with cell death such as LC3-II and other proteins in U251 cells
ChemoSen↑, The combined CUR and temozolomide treatment resulted in enhanced toxicity in U-87 glioblastoma cells.
NF-kB↓, suppression of NF-kappaB activity
CSCs↓, Dendrosomal curcumin increased the expression of miR-145 and decreased the expression of stemness genes including: NANOG, OCT4A, OCT4B1, and SOX2 [113]
Nanog↓,
OCT4↓,
SOX2↓,
eff↑, A synergistic interaction was observed when emodin and CUR were combined in terms of inhibition of cell growth, survival and invasion.
Sp1/3/4↓, CUR inducing ROS which results in suppression of specificity protein expression (SP1, SP3 and SP4) as well as miR-27a.
miR-27a-3p↓,
ZBTB10↑, downregulation of miR-27a by CUR, increased expression of ZBTB10 occurred
SOX9?, This resulted in decreased SOX9 expression.
ChemoSen↑, CUR used in combination with cisplatin resulted in a synergistic cytotoxic effect, while the effects were additive or sub-additive in combination with doxorubicin
VEGF↓, Some of the effects of CUR treatment are inhibition of NF-κB activity and downstream effector proteins, including: VEGF, MMP-9, XIAP, BCL-2 and Cyclin-D1.
XIAP↓,
Bcl-2↓,
cycD1/CCND1↓,
BioAv↑, Piperine is an alkaloid found in the seeds of black pepper (Piper nigrum) and is known to enhance the bioavailability of several therapeutic agents, including CUR
Hif1a↓, CUR inhibits HIF-1 in certain HCC cell lines and in vivo studies with tumor xenografts. CUR also inhibited EMT by suppressing HIF-1alpha activity in HepG2 cells
EMT↓,
BioAv↓, CUR has a poor solubility in aqueous enviroment, and consequently it has a low bioavailability and therefore low concentrations at the target sites.
PTEN↑, CUR treatment has been shown to result in activation of PTEN, which is a target of miR-21.
VEGF↓, CUR treatment resulted in a decrease of VEGF and activated Akt.
Akt↑,
EZH2↓, CUR also suppressed EZH2 expression by induction of miR-let 7c and miR-101.
NOTCH1↓, The expression of NOTCH1 was inhibited upon EZH2 suppression [
TP53↑, CUR has been shown to activate the TP53/miR-192-5p/miR-215/XIAP pathway in NSCLC.
NQO1↑, CUR can also induce the demethylation of the nuclear factor erythroid-2 (NF-E2) related factor-2 (NRT2) gene which in turn activates (NQO1), heme oxygenase-1 (HO1) and an antioxidant stress pathway which can prevent growth in mouse TRAMP-C1 prostate
HO-1↑,

672-

EGCG,

Molecular Targets of Epigallocatechin—Gallate (EGCG): A Special Focus on Signal Transduction and Cancer

Review,

NA,

DNMT1↓,
HDAC↓, HDAC1, HDAC2
G9a↓,
PRC2↓,
DNMT3A↓,
67LR↓, anti-proliferative action of EGCG is mediated by the binding to 67LR, whose expression is increased in tumour cells.
Apoptosis↑,
TumCCA↑,

3428-

EGCG,

Thymoquinone Is a Multitarget Single Epidrug That Inhibits the UHRF1 Protein Complex

Review,

Var,

TumCCA↑, Our previous work revealed that epigallocatechin-3-gallate (EGCG) induced cell cycle arrest and apoptosis in Jurkat cells by the downregulation of UHRF1 and DNMT1, and the upregulation of the tumor suppressor p16
UHRF1↓,
DNMT1↓,
p16↑,

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↑,

3236-

EGCG,

Buty,

Molecular mechanisms for inhibition of colon cancer cells by combined epigenetic-modulating epigallocatechin gallate and sodium butyrate

in-vitro,

Colon,

RKO

in-vitro,

Colon,

HCT116

in-vitro,

Colon,

HT29

Apoptosis↑, combination treatment induced apoptosis and cell cycle arrest in RKO, HCT-116 and HT-29 colorectal cancer cells.
TumCCA?,
HDAC1↓, decrease in HDAC1, DNMT1, survivin and HDAC activity in all three cell lines.
DNMT1↓,
survivin↓,
HDAC↓,
P21↑, induction of p21 and an increase in nuclear factor kappa B (NF-κB)-p65.
NF-kB↑,
γH2AX↑, An increase in double strand breaks as determined by gamma-H2A histone family member X (γ-H2AX) protein levels
ac‑H3↑, induction of histone H3 hyperacetylation was also observed with combination treatment.
DNAdam↑,

1503-

EGCG,

Epigenetic targets of bioactive dietary components for cancer prevention and therapy

Review,

NA,

IC50 values ranging from 0.21 to 0.47 μM

selectivity↑, EGCG has been shown to induce apoptosis and cell cycle arrest in many cancer cells without affecting normal cells
DNMT1↓, inhibition of DNMT1 leading to demethylation and reactivation of methylation-silenced genes.
RECK↑, EGCG-induced epigenetic reactivation of RECK
MMPs↓, negatively regulates matrix metalloproteinases (MMPs)
TumCI↓, inhibits tumor invasion, angiogenesis, and metastasis
angioG↓,
TumMeta↓,
HATs↓, EGCG has strong HAT inhibitory activity
IκB↑, increases the level of cytosolic IκBα
NF-kB↓, suppresses tumor necrosis factor α-induced NF-κB activation
IL6↓,
COX2↓,
NOS2↓,
ac‑H3↑, increased the levels of acetylated histone H3 (LysH9/18) and H4 levels
ac‑H4↑,
eff↑, EGCG may synergize with the HDAC inhibitory action of vorinostat to help de-repress silenced tumor suppressor genes regulating key functions such as proliferation and cell survival

4234-

H2,

Hydrogen gas alleviates sepsis-induced neuroinflammation and cognitive impairment through regulation of DNMT1 and DNMT3a-mediated BDNF promoter IV methylation in mice

in-vivo,

Sepsis,

 septic mice.

*cognitive↑, 2% H2 protects against sepsis-induced cognitive impairment in septic mice.
*DNMT1↓, 2% H2 decreases DNMT1, DNMT3a but not DNMT3b levels in the hippocampus.
*DNMT3A↓,
*BDNF↑, 2% H2 enhances BDNF levels through hypomethylating the BDNF promoter IV.

2915-

LT,

Luteolin promotes apoptotic cell death via upregulation of Nrf2 expression by DNA demethylase and the interaction of Nrf2 with p53 in human colon cancer cells

in-vitro,

Colon,

HT29

30 μM

in-vitro,

CRC,

SNU-407

30 μM

in-vitro,

Nor,

FHC

65 μM

DNMTs↓, luteolin inhibited the expression of DNA methyltransferases, a transcription repressor, and increased the expression and activity of ten-eleven translocation (TET) DNA demethylases,
TET1↑,
NRF2↑, luteolin decreased the methylation of the Nrf2 promoter region, which corresponded to the increased mRNA expression of Nrf2
HDAC↓, Recently, Zao et al. demonstrated that luteolin epigenetically activates the Nrf2 pathway by downregulating DNA methyltransferase (DNMT) and histone deacetylase (HDAC) expression
tumCV↓, Luteolin decreased the viability of all three cell lines in a dose-dependent manner
BAX↑, luteolin upregulated the expression of the apoptotic protein Bax, active caspase-9, and active caspase-3, while it downregulated the expression of the anti-apoptotic protein Bcl-2,
Casp9↑,
Casp3↑,
Bcl-2↓,
ROS↓, Luteolin promotes ROS scavenging by inducing the expression of antioxidant enzymes
GSS↑, luteolin increased the protein expression of the antioxidant enzymes GCLc, GSS, catalase, and HO-1 in a dose- and time-dependent manner
Catalase↑,
HO-1↑,
DNMT1↓, Luteolin markedly decreased the protein expression of DNMT1, DNMT3A, and DNMT3B in a dose- and time-dependent manner
DNMT3A↓,
TET1↑, In contrast, it markedly increased the protein expression of TET1, TET2, and TET3 in a dose- and time-dependent manner
TET3↑,
TET2↓,
P53↑, Luteolin upregulated the expression of p53 and its target p21 in a dose- and time-dependent manner
P21↑,

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

 100, 150 uM

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↓,

3357-

QC,

The polyphenol quercetin induces cell death in leukemia by targeting epigenetic regulators of pro-apoptotic genes

in-vitro,

AML,

HL-60

NA,

U937

DNMT1↓, Qu treatment almost eliminates DNMT1 and DNMT3a expression, and this regulation was in part STAT-3 dependent.
DNMT3A↓,
HDAC↓, The treatment also downregulated class I HDACs.
ac‑H3↑, Qu (50 μmol/L) treatment of cell lines for 48 h caused accumulation of acetylated histone 3 and histone 4, resulting in three- to ten fold increases in the promoter region of DAPK1, BCL2L11, BAX, APAF1, BNIP3, and BNIP3L.
ac‑H4↑,
BAX↑,
APAF1↑,
BNIP3↑,
STAT3↑, Quercetin downregulates DNMTs and STAT3

3193-

SFN,

Epigenetic Therapeutics Targeting NRF2/KEAP1 Signaling in Cancer Oxidative Stress

Review,

Var,

DNMTs↓, SFN, a natural phytochemical, primarily attenuates both DNMTs and HDACs, individually suppressing DNA hypermethylation and histones deacetylation, ultimately upregulating NRF2.
HDAC↑,
NRF2↑,
DNMT1↓, significant attenuation of DNMT1 and DNMT3a contributed to a decrease in the methylated CpG ratio in the NFE2L2 promoter region in an SFN dose- and time-dependent manner, thus increasing NRF2
DNMT3A↓,
NQO1↑, consequently increasing the transcription of its target genes such as NQO1 and catechol-O-methyltransferase (COMT)
COMT↑,
TumCG↓, SFN may prevent or slow the growth of recurrent prostate cancer, essentially without severe adverse events.
*toxicity↓,

3660-

SFN,

Sulforaphane - role in aging and neurodegeneration

Review,

AD,

*antiOx↑, antioxidant and anti-inflammatory responses by inducing Nrf2 pathway and inhibiting NF-κB
*Inflam↓,
*NRF2↑, increased Nrf2 expression and nuclear localization after SFN treatment
*NF-kB↓,
*HDAC↓, inhibiting HDAC and DNA methyltransferases a
*DNMTs↓,
*neuroP↑, prevent neurodegeneration.
*AntiAge↑, “miraculous” drug to prevent aging and neurodegeneration.
*DNMT1↓, decrease the expression of DNA methyltransferases (DNMTs), especially DNMT1 and DNMT3b.
*DNMT3A↓,
*memory↑, SFN prevented the memory impairment induced by OKA in rats.
*HO-1↑, restored Nrf2 and antioxidant protein (GCLC, HO-1) expression
*ROS↓, diminished the oxidative stress by attenuating ROS and NO levels, and increased GSH concentration.
*NO↓,
*GSH↑,
*NF-kB↓, reducing NF-κB and TNF-α, and by rising IL-10
*TNF-α↓,
*IL10↑,

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

978-

SIL,

A comprehensive evaluation of the therapeutic potential of silibinin: a ray of hope in cancer treatment

Review,

NA,

10uM

 200 to 570 μM

PI3K↓,
Akt↓,
NF-kB↓,
Wnt/(β-catenin)↓,
MAPK↓,
TumCP↓,
TumCCA↑, G0/G1 cell cycle arrest
Apoptosis↑, In T24 and UM-UC-3 human bladder cancer cells, silibinin treatment at a concentration of 10 μM significantly inhibited proliferation, migration, invasion, and induced apoptosis.
p‑EGFR↓,
JAK2↓,
STAT5↓,
cycD1/CCND1↓,
hTERT/TERT↓,
AP-1↓,
MMP9↓,
miR-21↓,
miR-155↓,
Casp9↑,
BID↑,
ERK↓, ERK1/2
Akt2↓,
DNMT1↓,
P53↑,
survivin↓,
Casp3↑,
ROS↑, cytotoxicity of silibinin in Hep-2 cells was associated with the accumulation of intracellular reactive oxygen species (ROS), which could be mitigated by the ROS scavenger NAC.

2197-

SK,

Shikonin derivatives for cancer prevention and therapy

Review,

Var,

ROS↑, This compound accumulates in the mitochondria, which leads to the generation of reactive oxygen species (ROS), and deregulates intracellular Ca2+ levels.
Ca+2↑,
BAX↑, shikonin alone by increasing the expression of the pro-apoptotic Bax protein and decreasing the expression of the anti-apoptotic Bcl2 protein
Bcl-2↓,
MMP9↓, This treatment also inhibited metastasis by decreasing the expression of MMP-9 and NF-kB p65 without affecting MMP-2 expression.
NF-kB↓,
PKM2↓, Figure 4
Hif1a↓,
NRF2↓,
P53↑,
DNMT1↓,
MDR1↓,
COX2↓,
VEGF↓,
EMT↓,
MMP7↓,
MMP13↓,
uPA↓,
RIP1↑,
RIP3↑,
Casp3↑,
Casp7↑,
Casp9↑,
P21↓,
DFF45↓,
TRAIL↑,
PTEN↑,
mTOR↓,
AR↓,
FAK↓,
Src↓,
Myc↓,
RadioS↑, shikonin acted as a radiosensitizer because of the high ROS production it induced.

2183-

SK,

Shikonin Inhibites Migration and Invasion of Thyroid Cancer Cells by Downregulating DNMT1

in-vitro,

Thyroid,

TPC-1

0.744 μg/mL

TumCMig↓, Shikonin inhibited TPC-1 cell migration and invasion in a dose-dependent manner
TumCI↓,
PTEN↑, The methylation of PTEN was suppressed by shikonin (increased the expression of PTEN)
DNMT1↓, which also reduced the expression of DNMT1

1002-

SSE,

Osi,

Adag,

Selenite as a dual apoptotic and ferroptotic agent synergizes with EGFR and KRAS inhibitors with epigenetic interference

in-vitro,

Lung,

H1975

7uM@72hr

in-vitro,

Lung,

H385

6uM@72hr

Apoptosis↑,
Ferroptosis↑,
DNMT1↓,
TET1↑,
TumCCA↑, G2/M arrest
cl‑PARP↑,
cl‑Casp3↑, H1975 cells only
Cyt‑c↑,
BIM↑,
NOXA↑,
Apoptosis↑,
ROS↑, Selenite is associated with oxidative stress
ER Stress↑, H1975 cells only
UPR↑, H1975 cells only

2104-

TQ,

The Potential Role of Nigella sativa Seed Oil as Epigenetic Therapy of Cancer

in-vitro,

BC,

MCF-7

in-vitro,

Cerv,

HeLa

TumCP↓, BSO significantly inhibited the proliferation of MCF-7, HeLa and Jurkat cells in a dose-dependent manner, and it induced apoptosis in these cell lines.
Apoptosis↑,
UHRF1↓, BSO-induced inhibitory effects were associated with a significant decrease in mRNA expression of UHRF1, DNMT1 and HDAC1
DNMT1↓,
HDAC1↓,
eff↝, A recent report showed that BSO content of TQ can vary from as low as 0.01 mg/g to 13.30 mg/g

3407-

TQ,

Thymoquinone and its pharmacological perspective: A review

Review,

NA,

*antiOx↑, TQ has been reported for its antioxidant properties to combat oxidative stress in several literatures
*ROS↓, scavenges the highly reactive oxygen
*GSTs↑, induction of glutathione transferase and quinone reductase
*GSR↑,
*GSH↑, TQ induces the Glutathione production with simultaneous inhibition of superoxide radical production
*RenoP↑, Improved renal function against mercuric chloride, doxorubicin and cisplatin damage have been reported through TQ based induction of Glutathione
*IL1β↓, Decreased the levels of IL-1β, TNFα, MMP-13, cox-2 and PGE(2)
*TNF-α↓,
*MMP13↓,
*COX2↓, reducing COX-2 gene expression, it also inhibited colon cancer cell migration.
*PGE2↓,
*radioP↑, Normal cell protection from ionizing radiation in cancer cell treatment.
Twist↓, TQ treatment have evidenced the inhibition of TWIST1 promoter activity and reduces it expression in cancer cell line leading inhibition of epithelial-mesenchymal transition mediated metastasis
EMT↓,
NF-kB↓, inhibiting the NF-κB expression in breast cancer model of mice
p‑PI3K↓, TQ (20 M) decreased the activation of prostaglandin receptors EP2 and EP4 in LoVo colon cancer cells by reducing p-PI3K, p-Akt, p-GSK3, and -catenin.
p‑Akt↓,
p‑GSK‐3β↓,
DNMT1↓, TQ's anticancer effects are mediated by DNMT1-dependent (dependent DNA methylation mediates) DNA methylation,
HDAC↓, inhibiting histone deacetylase (HDAC)

3424-

TQ,

Thymoquinone Is a Multitarget Single Epidrug That Inhibits the UHRF1 Protein Complex

Review,

Var,

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,

24 h with 20 µM of TQ

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

3427-

TQ,

Chemopreventive and Anticancer Effects of Thymoquinone: Cellular and Molecular Targets

ROS⇅, It appears that the cellular and/or physiological context(s) determines whether TQ acts as a pro-oxidant or an anti-ox- idant in vivo
Fas↑, Figure 2, cell death
DR5↑,
TRAIL↑,
Casp3↑,
Casp8↑,
Casp9↑,
P53↑,
mTOR↓,
Bcl-2↓,
BID↓,
CXCR4↓,
JNK↑,
p38↑,
MAPK↑,
LC3II↑,
ATG7↑,
Beclin-1↑,
AMPK↑,
PPARγ↑, cell survival
eIF2α↓,
P70S6K↓,
VEGF↓,
ERK↓,
NF-kB↓,
XIAP↓,
survivin↓,
p65↓,
DLC1↑, epigenetic
FOXO↑,
TET2↑,
CYP1B1↑,
UHRF1↓,
DNMT1↓,
HDAC1↓,
IL2↑, inflammation
IL1↓,
IL6↓,
IL10↓,
IL12↓,
TNF-α↓,
iNOS↓,
COX2↓,
5LO↓,
AP-1↓,
PI3K↓, invastion
Akt↓,
cMET↓,
VEGFR2↓,
CXCL1↓,
ITGA5↓,
Wnt↓,
β-catenin/ZEB1↓,
GSK‐3β↓,
Myc↓,
cycD1/CCND1↓,
N-cadherin↓,
Snail↓,
Slug↓,
Vim↓,
Twist↓,
Zeb1↓,
MMP2↓,
MMP7↓,
MMP9↓,
JAK2↓, cell proliferiation
STAT3↓,
NOTCH↓,
cycA1/CCNA1↓,
CDK2↓,
CDK4↓,
CDK6↓,
CDC2↓,
CDC25↓,
Mcl-1↓,
E2Fs↓,
p16↑,
p27↑,
P21↑,
ChemoSen↑, Such chemo-potentiating effects of TQ in different cancer cells have been observed with 5-fluorouracil in gastric cancer and colorectal cancer models

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↓,

3429-

TQ,

Thymoquinone exerts potent growth-suppressive activity on leukemia through DNA hypermethylation reversal in leukemia cells

in-vitro,

AML,

in-vivo,

NA,

mouse

DNMT1↓, Further, exposure of leukemia cell lines and patient primary cells to TQ resulted in DNMT1 downregulation, mechanistically, through dissociation of Sp1/NFkB complex from DNMT1 promoter.
Sp1/3/4↓,
NF-kB↓,
Apoptosis↑, led to a reduction of DNA methylation, a decrease of colony formation and an increase of cell apoptosis via the activation of caspases.
Casp↑,
Bcl-xL↓, been shown to downregulate the expression of Bcl-xL [18], COX-2 [19], iNOS [20], 5-LOX [21], TNF [22] and cyclin D1 [16]
COX2↓,
iNOS↓,
5LO↓,
TNF-α↓,
cycD1/CCND1↓,
BioAv↝, The stability data revealed that the compound was stable at −20°C under dim light condition, but not at 25°C and 37°C. Thus, TQ is more stable in the dark and at cold temperature.
TumCG↓, TQ administration attenuates leukemia growth in mice

3423-

TQ,

Epigenetic role of thymoquinone: impact on cellular mechanism and cancer therapeutics

Review,

Var,

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 41 of 41

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 41

Pathway results for Effect on Cancer / Diseased Cells:

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

antiOx?, 1, antiOx↑, 4, Catalase↑, 1, Ferroptosis↓, 1, GPx↑, 1, GSH↑, 3, GSR↑, 1, GSTs↑, 1, HO-1↑, 1, MDA↓, 2, NRF2↑, 2, ROS↓, 5, SOD↑, 2,

Core Metabolism/Glycolysis ⓘ

NAD↑, 1, SIRT1↑, 1,

Cell Death ⓘ

Ferroptosis↓, 1, MCT1↓, 1,

DNA Damage & Repair ⓘ

DNMT1↓, 5, DNMT3A↓, 3, DNMTs↓, 2,

Proliferation, Differentiation & Cell State ⓘ

HDAC↓, 3, HDAC3↓, 1, KLF4↑, 1,

Migration ⓘ

Ki-67↓, 1, MMP13↓, 1,

Angiogenesis & Vasculature ⓘ

NO↓, 2, NO↑, 1,

Barriers & Transport ⓘ

GastroP↑, 1, IBI↑, 1,

Immune & Inflammatory Signaling ⓘ

COX2↓, 1, CRP↓, 1, IL10↑, 1, IL1β↓, 2, IL6↓, 1, Inflam↓, 5, NF-kB↓, 3, PGE2↓, 1, TNF-α↓, 3,

Synaptic & Neurotransmission ⓘ

BDNF↑, 1,

Protein Aggregation ⓘ

Aβ↓, 1,

Drug Metabolism & Resistance ⓘ

BioAv↓, 1, BioAv↑, 3, eff↑, 1,

Clinical Biomarkers ⓘ

CRP↓, 1, GutMicro↑, 1, IL6↓, 1, Ki-67↓, 1,

Functional Outcomes ⓘ

AntiAge↑, 1, AntiCan↑, 1, cardioP↑, 1, cognitive↑, 2, hepatoP↑, 1, memory↑, 2, neuroP↑, 2, Obesity↓, 1, radioP↑, 1, RenoP↑, 3, toxicity↓, 2,

Infection & Microbiome ⓘ

Bacteria↓, 1,
Total Targets: 59

Scientific Paper Hit Count for: DNMT1, DNA (cytosine-5-)-methyltransferase 1

8 Thymoquinone
6 Sulforaphane (mainly Broccoli)
5 Berberine
5 EGCG (Epigallocatechin Gallate)
4 Curcumin
2 Quercetin
2 Shikonin
1 Allicin (mainly Garlic)
1 alpha Linolenic acid
1 Apigenin (mainly Parsley)
1 Ashwagandha(Withaferin A)
1 Capsaicin
1 Chlorogenic acid
1 Butyrate
1 Hydrogen Gas
1 Luteolin
1 Silymarin (Milk Thistle) silibinin
1 Selenite (Sodium)
1 Osimertinib
1 Adagrasib

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#:85  State#:%  Dir#:1
  wNotes=on  sortOrder:rid,rpid

DNMT1 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 ⓘ

Cellular Microenvironment ⓘ

Protein Aggregation ⓘ

Hormonal & Nuclear Receptors ⓘ

Drug Metabolism & Resistance ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

Core Metabolism/Glycolysis ⓘ

Cell Death ⓘ

DNA Damage & Repair ⓘ

Proliferation, Differentiation & Cell State ⓘ

Migration ⓘ

Angiogenesis & Vasculature ⓘ

Barriers & Transport ⓘ

Immune & Inflammatory Signaling ⓘ

Synaptic & Neurotransmission ⓘ

Protein Aggregation ⓘ

Drug Metabolism & Resistance ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

Infection & Microbiome ⓘ

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