HATs Cancer Research Results
HATs, histone acetyltransferases: Click to Expand ⟱
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Histone acetyltransferases (HATs) are a family of enzymes that play a crucial role in the regulation of gene expression by modifying chromatin structure. HATs transfer acetyl groups to the lysine residues of histone proteins, which are the main components of chromatin. This modification, known as histone acetylation, leads to the relaxation of chromatin structure, allowing for increased access of transcription factors to DNA and promoting gene expression.
HATs is overexpressed in cancers with poor prognosis.
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Scientific Papers found: Click to Expand⟱
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MDA-MB-231 |
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Nor, |
HUVECs |
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MCF7 |
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T47D |
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in-vitro, |
BC, |
BT549 |
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MDA-MB-361 |
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TumCP↓,
COX2/PTGS2↓, suppress COX-2 expression at both protein and mRNA levels.
*angioG↓,
Cyt‑c↑,
CREB2↓, inhibited the binding of the transactivators CREB2, C-Fos and NF-κB
cFos↓,
NF-kB↓,
HATs↓,
cl‑Casp3↑,
cl‑Casp9↑,
Bax:Bcl2↑,
Apoptosis↑,
*toxicity↓, IC50: 50uM for normal vs 20-35uM for cancer cells
*CRM↑, Altogether, these findings identify aspirin as an evolutionary conserved CRM.
*HATs↓, inhibit the acetyltransferase activity of EP300
*NF-kB↓, aspirin reportedly inhibits the activation of the pro-inflammatory transcription factor nuclear factor kappa light-chain enhancer of activated B cell (NF-κB)
*EP300↓, Salicylate Inhibits EP300 Acetyltransferase by Competing with AcCoA
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Review, |
AD, |
NA |
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Review, |
Park, |
NA |
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*neuroP↑, Curcumin has an outstanding safety profile and a number of pleiotropic actions with potential for neuroprotective efficacy, including anti-inflammatory, antioxidant, and anti-protein-aggregate activities.
*Inflam↓,
*antiOx↑,
*BioAv↓, despite concerns about poor oral bioavailability, curcumin has at least 10 known neuroprotective action
*AP-1↓, Curcumin inhibition of AP-1 and NF-κB-mediated transcription occurs at relatively low (<100 nM) doses and might be due to inhibition of histone acetylase (HAT) or activation of histone deacetylase (HDAC) activity
*NF-kB↓,
*HATs↓,
*HDAC↑,
Dose↑, At high doses (>3 µM) that are relevant to colon cancer but unlikely achievable with oral delivery in plasma and tissues outside of the gut, curcumin can act as an alkylating agent,10 a phase II enzyme inducer,11 and stimulate antioxidant response el
*ROS↓, We also found that curcmin reduced oxidative damage, inflammation, and cognitive deficits in rats receiving CNS infusions of toxic Aβ
*cognitive↑,
*Aβ↓, dose-dependently blocked Aβ aggregation at submicromolar concentrations
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
*antiOx↑, Curcumin exerts potent antioxidant, anti-inflammatory, and anticancer effects by modulating multiple signaling pathways, including NF-κB, PI3K/Akt, and Wnt/β-catenin.
*Inflam↓,
*BioAv↓, curcumin’s clinical application is limited by poor solubility, rapid metabolism, and low systemic bioavailability.
NF-kB↓, graphical abstract
PI3K↓,
Akt↓,
Wnt↓,
β-catenin/ZEB1↓,
DNMTs↓,
TumCI↓,
TumMeta↓,
*BioAv↑, Advanced drug delivery systems such as nanoparticles, liposomes, and micelles have been developed to address these challenges. These systems enhance curcumin’s solubility, stability, and targeted delivery, improving therapeutic efficacy while minimiz
*BioAv↑, coadministration with piperine, lipid-based formulations, and nanoparticle microencapsulation have been developed. Piperine has been shown to increase curcumin absorption by up to 2000 percent
angioG↓, Curcumin is also known for its antiangiogenic action through its inhibitory activity against vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs)
VEGF↓,
MMPs↓,
*ROS↓, suppresses oxidative stress by scavenging free radicals and enhancing the activity of endogenous antioxidant enzymes such as superoxide dismutase (SOD) and catalase
*SOD↑,
*Catalase↑,
*GSTs↑, timulating phase II detoxifying enzymes such as glutathione S-transferase (GST), UDP-glucuronosyltransferase, and heme oxygenase-1 (HO-1).
*HO-1↑,
*NRF2↑, It also enhances the activity of the transcription factor Nrf2, which regulates genes crucial for cellular redox homeostasis and safeguarding cells against oxidative damage
mTOR↓, 0 to 50 μM, treatment was associated with decreased phosphorylation of Akt kinase (Akt), mammalian target of rapamycin (mTOR), glycogen synthase kinase (GSK3β), Forkhead box protein O1 (FOXO1), and other proteins
GSK‐3β↓,
FOXO1↓,
*radioP↑, Reduced radiation-induced dermatitis and inflammatory cytokine expression (IL-1, IL-6, TNF-α)
*IL1↓,
*IL6↓,
*TNF-α↓,
HATs↓, curcumin has been described as an agent that reduces histone acetylation by inhibiting HAT (histone acetyltransferases), such as the p300/CBP family of proteins
HDAC↓, curcumin has been detected to be an HDI and has the ability to inhibit the expressions of HDACs, like HDAC1, HDAC3, and HDAC8,
ROS↑, Elevating the levels of reactive oxygen species (ROS) in colon adenocarcinoma cells is one of the outcomes of treatment with curcumin, which results in a decline in cell proliferation and viability
ROS↑, at higher concentrations or in the presence of transition metal ions (e.g. Cu2+, Fe2+/Fe3+), curcumin can paradoxically act as a pro-oxidant.
MMP↓, Excess ROS damages mitochondrial membranes, oxidizes nucleic acids, lipids, and proteins, and activates apoptotic cascades via cytochrome c release and caspase activation
Casp↑,
Cyt‑c↑,
COX1↓, curcumin acts as a partial and condition-dependent inhibitor of both COX-1 and COX-2.
COX2/PTGS2↓,
PGE2↓, At lower or therapeutic concentrations, curcumin predominantly downregulates COX-2 and reduces prostaglandin E2 (PGE2) synthesis.
*cytoP450↓, curcumin’s capacity to inhibit cytochrome P450 enzymes may influence the metabolism of numerous medicines over extended durations.
ChemoSen↑, curcumin has been integrated with standard chemotherapy agents, including doxorubicin, cisplatin, and paclitaxel, to enhance cancer treatment efficacy
cardioP↑, co-delivery of curcumin and doxorubicin via nanoparticles improved anticancer effectiveness and decreased cardiotoxicity.
eff↑, concurrent treatment of curcumin and resveratrol has demonstrated increased anti-inflammatory and anticancer properties
Telomerase↓, EGCG stimulates telomere fragmentation through inhibiting telomerase activity.
DNMTs↓, EGCG reduced DNMTs,
cycD1/CCND1↓, EGCG also reduced the protein expression of cyclin D1, cyclin E, CDK2, CDK4, and CDK6. EGCG also inhibited the activity of CDK2 and CDK4, and caused Rb hypophosphorylation
cycE/CCNE↓,
CDK2↓,
CDK4↓,
CDK6↓,
HATs↓, EGCG can inhibit certain biomedically important molecular targets such as DNMTs, HATs, and HDACs
HDAC↓,
selectivity↑, EGCG has shown higher cytotoxicity in cancer cells than in their normal counterparts.
uPA↓, EGCG blocks urokinase, an enzyme which is essential for cancer growth and metastasis
NF-kB↓, EGCG inhibits NFκB and expression of TNF-α, reduces cancer promotion
TNF-α↓,
*ROS↓, It acts as strong ROS scavenger and antioxidant,
*antiOx↑,
Hif1a↓, ↓ HIF-1α; ↓ VEGF; ↓ VEGFR1;
VEGF↓,
MMP2↓, ↓ MMP-2; ↓ MMP-9; ↓ FAK;
MMP9↓,
FAK↓,
TIMP2↑, TIMP-2; ↑
Mcl-1↓, ↓ Mcl-1; ↓ survivin; ↓ XIAP
survivin↓,
XIAP↓,
PCNA↓, ↓ PCNA; ↑ 16; ↑ p18; ↑ p21; ↑ p27; ↑ pRb; ↑ p53; ↑ mdm2
p16↑,
P21↑,
p27/CDKN1B↑,
pRB↑,
P53↑,
MDM2↑,
ROS↑, ↑ ROS; ↑ caspase-3; ↑ caspase-8; ↑ caspase-9; ↑ cytochrome c; ↑ Smac/DIABLO; ↓↑ Bax; Z Bak; ↓ cleaved PPAR;
Casp3↑,
Casp8↑,
Casp9↑,
Cyt‑c↑,
Diablo↑,
BAX⇅,
cl‑PPARα↓,
PDGF↓, ↓ PDGF; ↓ PDGFRb; ↓ EGFR;
EGFR↓,
FOXO↑, activated FOXO transcription factors
AP-1↓, The inhibition of AP-1 activity by EGCG was associated with inhibition of JNK activation but not ERK activation.
JNK↓,
COX2/PTGS2↓, EGCG reduces the activity of COX-2 following interleukin-1A stimulation of human chondrocytes
angioG↓, EGCG inhibits angiogenesis by enhancing FOXO transcriptional activity
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/PTGS2↓,
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
*NF-kB↓, GA Inhibits Signaling of Nuclear Factor-Kappa B (NF-jB)
PI3K↓, GA Inhibits Phosphatidylinositol 3′-Kinase/Protein Kinase B (PI3K/Akt)
Akt↓,
STAT3↓, table 15.1 GA Inhibits Signal Transducer and Activator of Transcription-3 (STAT-3) Pathways
STAT5↓,
IL6↓,
COX2/PTGS2↓, GA Inhibits COX-2
iNOS↓, GA Inhibits iNOS
MMPs↓,
Src↓, GA Inhibits Src
PKA↓,
CXCR4↑, GA Inhibits Chemokine X-Receptor 4 (CXCR4) and Downstream Signaling Pathways
VEGF↓,
Bcl-2↓, GA Inhibits the Expression of Bcl-2 Family Proteins
Bcl-xL↓,
IAP1↓,
Mcl-1↓,
survivin↓,
cycD1/CCND1↓, GA Inhibits Expression of Cyclin D1
HSP90↓,
HSP70/HSPA5↓,
MAPK↓, GA Inhibits Mitogen-Activated Protein Kinase (MAPK)
HATs↓, GA Inhibits CBP/p300 Histone Aceyltransferase (HAT) and Histone Deacetylase (HDAC)
HDAC↓,
FAK↓, GA Inhibits the Activation of Focal Adhesion Kinase (FAK)
ROS↑, GA Induces the Production of Reactive Oxygen Species (ROS)
MMP7↓, GA Inhibits Matrix Metalloproteinase 7 & 9 (MMP-7 & 9)
MMP9↓,
α-tubulin↑, GA Inhibits Tubulin
cl‑PARP↑, GA Induces Cleavage of Poly(ADP-Ribose) Polymerases (PARPs)
TNF-α↓, GA Inhibits Tumor Necrosis Factor-a (TNF-a)
BID↑, GA Induces BID
BAD↑, GA Induces BAD
Cyt‑c↑, GA, induces the expression of cytochrome c in colorectal cancer HT-29, bladder cancer T24 and UMUC3, breast cancer MDA-MB-231, and human hepatocellular carcinoma cells
Casp3↑, GA Induces the Activation of Caspase-3 and Caspase-9
Casp9↑,
*AntiArt↑, GA inhibits RA by inhibiting the levels of cytokines and key inflammatory molecules [
*antiPs↑, recent study showed that GA could be used as an anti-psoriatic agent
HATs↓, Its activities include inhibition of histone acetyltransferases (HATs)
p300↓, By inhibiting HAT enzymes such as p300/CBP and PCAF, garcinol affects the acetylation status of multiple transcription factors and histones,
CBP↓,
NF-kB↓, including NF-κB, STAT3, PI3K/AKT, MAPK, and Wnt/β-catenin, resulting in the suppression of inflammation, angiogenesis, proliferation, and metastasis.
STAT3↓, inhibition of NF-kB, STAT 3, P13/Akt, COX-2, MAPK pathways
PI3K↓,
Akt↓,
MAPK↓,
Wnt↓,
β-catenin/ZEB1↓,
Inflam↓,
angioG↓,
TumCP↓,
TumMeta↓,
TumCCA↑, figure 3
EMT↓, inhibition of epithelial-to-mesenchymal transition (EMT), and cancer stem cell targeting.
CSCs↓,
P53↑, garcinol activates tumor-suppressor proteins such as p53 and inhibits thioredoxin reductase, resulting in elevated intracellular reactive oxygen species (ROS).
TrxR↓,
ROS↑,
JNK↑, The accumulation of ROS subsequently stimulates JNK activation and DNA damage signaling, reinforcing p53 function and promoting apoptosis rather than mere growth inhibition
DNAdam↑,
mt-Apoptosis↑, showing activation of mitochondrial apoptosis through the ROS/JNK/ATF-2/Bcl-2 axis
ER Stress↑, In rhabdomyosarcoma cells, garcinol was also shown to trigger endoplasmic reticulum (ER) stress, elevating the expression of stress-responsive genes such as DDIT3, DDIT4, TRIB3, and SESN2, which facilitate apoptosis under prolonged stress [
CHOP/DDIT3↑,
DDIT4↑,
TRIB3↑,
SESN2↑,
miR-218↑, garcinol upregulates let-c family miRNAs and miR-218 in breast cancer and NSCLC cells by the suppression of EMT and stemness
eff↑, When combined with HDAC inhibitors such as SAHA (Suberoylanilide Hydroxamic Acid), also known by its clinical name Vorinostat, garcinol provides complementary effects on maintaining histone acetylation balance,
ChemoSen↑, when used alongside chemotherapeutic agents such as doxorubicin or cisplatin, garcinol sensitizes resistant tumor cells by restoring apoptotic gene expression and overcoming drug resistance mechanisms
BioAv↓, garcinol suffers from poor aqueous solubility, rapid metabolism, and limited bioavailability,
Half-Life↓,
BioAv↑, These nanoformulations have demonstrated enhanced cellular uptake, prolonged plasma half-life, and superior cytotoxicity in breast, colon, and lung cancer models compared with free garcinol
AntiCan↑, garcinol has demonstrated huge potential as an anti-cancer agent, inhibiting tumor growth, progression, and metastasis in various cancers, such as lung, liver, pancreas, prostate, breast, colon, and brain cancers.
TumCG↓,
TumMeta↓,
toxicity↓, garcinol offers a safer alternative with broad-spectrum activity and minimal adverse effects.
Apoptosis↑, anti-tumorigenic properties are linked to apoptosis induction, angiogenesis inhibition, and modulation of the tumor microenvironment
angioG↓,
*BioAv↝, nano-delivery systems have improved its bioavailability and therapeutic efficacy, overcoming challenges related to its solubility and stability.
HATs↓, Garcinol primarily targets histone acetyltransferases (HATs), particularly p300 and CBP (CREB-binding protein), leading to structural modifications in these proteins.
p300↓,
CBP↓,
PI3K↓, Garcinol exerts its anticancer effects primarily by modulating key signaling pathways, including the PI3K/AKT, NF-κB, JAK/STAT, and MAPK pathways.
Akt↓,
NF-kB↓,
STAT↓,
mTOR↓, figure 1
DFF45↓,
survivin↓,
N-cadherin↓,
Twist↓,
MMP2↓,
MMP3↓,
MMP9↓,
Mcl-1↓,
EZH2↓,
NOTCH↓,
CXCR4↓,
PGE2↓,
VEGF↓,
mPGES-1↓,
CycB/CCNB1↓,
CDK2↓,
CDK4/6↓,
iNOS↓,
COX2/PTGS2↓,
IL1↓,
TNF-α↓,
PARP↑,
Bcl-2↓,
AChE↓, Garcinol has anticholinesterase activity toward acetyl cholinesterase (AChE) and butylcholinesterase.
BChE↓,
*Inflam↓, Garcinol is a direct and potent inhibitor of the catalytic activity of 2 crucial enzymes involved with inflammation, 5-lipoxygenase, and microsomal prostaglandin PGE2 synthase.
*5LO↓,
*PGE2↓,
*antiOx↑, Garcinol has free radical scavenging activity against the hypoxanthine/xanthine oxidase system, superoxide anion, hydroxyl radical, and methyl radical
FAK↓, Garcinol inhibited cell invasion by inhibiting the downstream signaling of FAK.
DNAdam↑, In human leukemia HL-60 cells, garcinol inhibited activity in a dose- and time-dependent manner by inducing DNA fragmentation and apoptotic cell death.
MMP↓, loss of mitochondrial membrane potential by garcinol-induced apoptosis.
Casp↑, Garcinol induced caspase-mediated apoptosis in highly metastatic human breast cancer cells (MDA-MD-231) through down-regulation of NF-kappaB signaling pathway
NF-kB↓,
HATs↓, Garcinol is a potent, nonspecific in vitro and in vivo inhibitor of HATS, a key regulatory step in gene expression in eukaryotic cells.
*toxicity↓, Most reports suggest dietary administration of garcinol in animal studies exhibits low toxicity, with animal studies finding no histological or pathological changes in liver, kidney, lung, heart, or esophageal organ systems.
antiOx↑, Garcinol action in cancer cells is based on its antioxidant and anti-inflammatory properties, but also on its potency to inhibit histone acetyltransferases (HATs).
Inflam↓,
HATs↓,
p300↓, Elevated levels of P300/CBP and PCAF have been reported in many malignancies.
CBP↓,
PCAF↓,
cycD1/CCND1↓, Garcinol decreased cyclin D1 and cyclin D3 expression, decreased STAT expression, and caused inhibition of the PI3K/AKT pathway, which is crucial for proliferation, invasion, and metastasis
STAT↓,
PI3K↓,
Akt↓,
TumCP↓,
TumCI↓,
TumMeta↓,
TumCCA↑, garcinol application resulted in cell cycle arrest and a marked decrease in cyclin-dependent kinase 2 (CDK2) and cyclin-dependent kinase 4 (CDK4) expression
CDK2↓,
CDK4↓,
antiOx↑, demonstrated to be anti-oxidant, anti-inflammatory and anti-cancer in nature.
Inflam↓,
AntiCan↑,
NF-kB↓, Garcinia indica has been found to be an effective inhibitor of several key regulatory pathways (e.g., NF-kB, STAT3 etc.) in cancer cells, thereby being able to control malignant growth of solid tumours in vivo.
STAT3↓,
antiNeop↑, Despite its high potential as an anti-neoplastic modulator of several cancer types such as head and neck cancer, breast cancer, hepatocellular carcinoma, prostate cancer, colon cancer etc.
5LO↓, ability of garcinol to bind and inhibit 5-lipoxygenase (5-Lox),
eff↑, . The addition of 10 % FBS (fetal bovine serum) to medium leads to approximately 10-fold decrease in IC 50 value of garcinol for HCT116 cell growth.
HATs↓, Garcinol has been demonstrated to inhibit HATs such as p300 and PCAF both in vitro and in vivo
p300↓,
PCAF↓,
miR-200c↑, Garcinol treatment has been shown to cause upregulation of several tumor suppressor miRNAs, of which miR-200c was found to target and downregulate Notch1 in pancreatic CSCs
NOTCH1↓,
CSCs↓,
COX2/PTGS2↓, garcinol has been shown to cause significant reduction in expression level of cyclooxygenase-2 (COX-2), cyclin D1, and vascular endothelial growth factor
cycD1/CCND1↓,
VEGF↓,
PI3K↓, via inhibition of the extracellular signal-regulated protein kinase 1/2, PI3K/Akt and Wnt/b-catenin
Akt↓,
Wnt↑,
β-catenin/ZEB1↓,
ROS↑, It could lead to accumulation of reactive oxygen species (ROS), endoplasmic reticulum (ER) stress modulator GADD153
CHOP/DDIT3↑,
Bax:Bcl2↑, increased Bax2/Bcl-2 ratio, elevated tBid (truncated Bid), and caspase 8 in cancer cell.
Casp8↑,
FAK↓, garcinol can lead to inhibition of tyrosine phosphorylation of focal adhesion kinase (FAK),
*neuroP↑, garcinol being considered in development of therapeutics for neurodegenerative diseases such as Alzheimers’s, Parkinson’s to attenuate oxidative stress-induced neurotoxicity.
PCNA↓, Significant reduction in proliferating cell nuclear antigen (PCNA) index in ACF was also observed with gar-
cinol treatment
*GSTs↑, Garcinol administration in such cases was also seen to enhance activities of liver glutathione S-transferase (GST) and quinone reductase (QR), which play an important role in detoxification process of body
*AChE↓, Garcinol, a polyisoprenylated benzophenone harvested from Garcinia indica, exerts anti-cholinesterase properties towards acetyl cholinesterase (AChE) and butyrylcholinesterase (BChE) with IC50s of 0.66 μM and 7.39 μM, respectively
*BChE↓,
*HATs↓, Garcinol also inhibits histone acetyltransferases (HATs, IC50= 7 μM) and p300/CPB-associated factor (PCAF, IC50 = 5 μM). Garcinol has anti-inflammatory and anti-cancer activity[2].
*Inflam↓,
AntiCan↑,
ERK↓, ERK1/2
PI3K/Akt↓,
Wnt/(β-catenin)↓,
STAT3↓,
NF-kB↓,
ChemoSen↑, cisplatin or paclitaxel, in the presence of garcinol can lead to a significant increase in the treatment outcome
COX2/PTGS2↓,
Casp3↑,
Casp9↑,
BAX↑,
Bcl-2↓,
VEGF↓,
TGF-β↓,
HATs↓,
E-cadherin↑,
Vim↓,
Zeb1↓,
ZEB2↓,
Let-7↑,
MMP9↓,
TumCCA↑, cycle arrest at G0/G1 phase
ROS↑,
MMP↓,
IL6↓,
NOTCH1↓,
antiNeop↑,
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KYSE150 |
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KYSE450 |
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HATs↓, Garcinol, a natural compound extracted from Gambogic genera, is a histone acetyltransferase (HAT) inhibitor
TumCCA↑,
Apoptosis↑,
TumCMig↓,
TumCI↓,
CBP↓,
p300↓,
TGF-β↓, suppressed TGF-β1-activated Smad and non-Smad pathway
Ki-67↓,
SMAD2↓,
SMAD3↓,
HATs↓, potent inhibitor of histone acetyltransferases p300 (IC50 approximately 7 microm)
PCAF↓,
Apoptosis↑,
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Lung, |
A549 |
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NA, |
HeLa |
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HATs↓, garcinol, a HAT inhibitor
other↑, Garcinol radiosensitized A549 lung and HeLa cervical carcinoma cells with dose enhancement ratios (at 10% surviving fraction) of 1.6 and 1.5, respectively
HATs↓, HAT inhibitor
BAX↑,
PARP↑, PARP (proapoptotic) expression
Bcl-2↓,
Casp3↑,
Casp9↑,
DR5↑,
cFLIP↓,
MMP2↓,
MMP9↓,
STAT3↓,
p‑Akt↓,
TumCMig↓, luteolin inhibited migration and colony formation in HeLa cells.
DNMTs↓, Luteolin decreased DNMT activity in HeLa cells in a concentration-dependent manner.
HDAC↓, Luteolin Decreases HDAC Activity in HeLa Cells
HATs↓, Luteolin Reduces the HAT Activity in a Dose-Dependent Manner
ac‑H3↓, H3 acetylation marks were diminished after treatment with the 20 µM of luteolin
ac‑H4↓, the acetylation marks at H4 were also modulated,
MMP2↓, Luteolin resulted in downregulation of expression of various proteins related to migration and inflammation in HeLa cells, and fold changes (FC) after treatment with 10 and 20 µM for 48 h are given, respectively, for MMP2 (FC 0.33, 0.26), MMP3 (FC 0.
MMP9↓,
HO-1↓, Genes related to cell proliferation, growth, and apoptosis such as BCL-X (FC 0.55, 0.45), HO-1/HMOX1 (FC 0.40, 0.25), Kallikrein6 (FC 0.55, 0.48), Kallikrein 3/PSA (FC 0.58, 0.48) were reduced.
E-cadherin↑, E-cadherin (FC 1.8, 2.9) were upregulated
EZH2↓, Luteolin has depicted increased expression of MiR-26a, which is a regulator of EZH2, and at the same time, it has inhibited EZH2
HER2/EBBR2↓, luteolin treatment decreased the inflammatory and migratory proteins such as MMp-2, MMP-3, HO-1/HMOX1, Her1, HER2, Her4, mesothelin, cathepsin B, MUC1, nectin 4, FOXC2, IL-18 BPa, CCL3/MIP-1α, CXCL8/IL-8, IL-2
IL18↓,
IL8↓,
IL2↓,
Apoptosis↑, Recent studies have demonstrated that Sulforaphane not only induces apoptosis and cell cycle arrest in BC cells, but also inhibits the growth, invasion, and metastasis of BC cells
TumCG↓,
TumCI↓,
TumMeta↓,
glucoNG↓, Additionally, it can inhibit BC gluconeogenesis
ChemoSen↑, demonstrate definite effects when combined with chemotherapeutic drugs/carcinogens.
TumCCA↑, SFN can block the cell cycle in G2/M phase, upregulate the expression of Caspase3/7 and PARP cleavage, and
downregulate the expression of Survivin, EGFR and HER2/neu
Casp3↑,
Casp7↑,
cl‑PARP↑,
survivin↓,
EGFR↓,
HER2/EBBR2↓,
ATP↓, SFN inhibits the production of ATP by inhibiting glycolysis and mitochondrial oxidative phosphorylation in BC cells in a dose-dependent manner
Glycolysis↓,
mt-OXPHOS↓,
AKT1↓, dysregulation of glucose metabolism by inhibiting the AKT1-HK2 axis
HK2↓,
Hif1a↓, Sulforaphane inhibits glycolysis by down-regulating hypoxia-induced HIF-1α
ROS↑, SFN can upregulate ROS production and Nrf2 activity
NRF2↑,
EMT↓, inhibiting EMT process through Cox-2/MMP-2, 9/ ZEB1 and Snail and miR-200c/ZEB1 pathways
COX2/PTGS2↓,
MMP2↓,
MMP9↓,
Zeb1↓,
Snail↓,
HDAC↓, FN modulates the histone status in BC cells by regulating specific HDAC and HATs,
HATs↓,
MMP↓, SFN upregulates ROS production, induces mitochondrial oxidative damage, mitochondrial membrane potential depolarization, cytochrome c release
Cyt‑c↓,
Shh↓, SFN significantly lowers the expression of key components of the SHH pathway (Shh, Smo, and Gli1) and inhibits tumor sphere formation, thereby suppressing the stemness of cancer cells
Smo↓,
Gli1↓,
BioAv↝, SFN is unstable in aqueous solutions and at high temperatures, sensitive to oxygen, heat and alkaline conditions, with a decrease in quantity of 20% after cooking, 36% after frying, and 88% after boiling
BioAv↝, It has been reported that the ability of individuals to use gut myrosinase to convert glucoraphanin
into SFN varies widely
Dose↝, Excitingly, it has been reported that daily oral administration of 200 μM SFN in melanoma patients can achieve plasma levels of 655 ng/mL with good tolerance
*EP300↓, potent autophagy inducers including spermidine de facto act as EP300 inhibitors.
*mTORC1↓, simultaneously inhibit mTORC1.
*CRM↑, caloric restriction or intermediate fasting,7 continuous or intermittent medication of rapamycin,8, 9, 10 administration of the sirtuin 1-activator resveratrol,11, 12 external supply of the polyamine spermidine,
*HATs↓, Spermidine turned out to be an efficient inhibitor of histone acetyltransferases in vitro
*p62↓, Moreover, all the mentioned acetyltransferase inhibitors induced a significant reduction of p62/SQSTM1 levels,
*AntiAge↑, Spermidine retards the manifestation of several major age-associated diseases including arterial aging,36 colon cancer37 and neurodegenerative processes in mice
AntiCan↑,
Showing Research Papers: 1 to 22 of 22
* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 22
Pathway results for Effect on Cancer / Diseased Cells:
NA, unassigned(tgid=0) ⓘ
DDIT4↑, 1,
Redox & Oxidative Stress(tgid=1) ⓘ
antiOx↑, 2, HO-1↓, 1, NRF2↑, 1, mt-OXPHOS↓, 1, ROS↑, 8, TrxR↓, 1,
Mitochondria & Bioenergetics(tgid=3) ⓘ
ATP↓, 1, MMP↓, 4, XIAP↓, 1,
Core Metabolism/Glycolysis(tgid=4) ⓘ
AKT1↓, 1, glucoNG↓, 1, Glycolysis↓, 1, HK2↓, 1, PI3K/Akt↓, 1, cl‑PPARα↓, 1,
Cell Death(tgid=5) ⓘ
Akt↓, 6, p‑Akt↓, 1, Apoptosis↑, 6, mt-Apoptosis↑, 1, BAD↑, 1, BAX↑, 2, BAX⇅, 1, Bax:Bcl2↑, 2, Bcl-2↓, 4, Bcl-xL↓, 1, BID↑, 1, Casp↑, 2, Casp3↑, 5, cl‑Casp3↑, 1, Casp7↑, 1, Casp8↑, 2, Casp9↑, 4, cl‑Casp9↑, 1, CBP↓, 4, cFLIP↓, 1, Cyt‑c↓, 1, Cyt‑c↑, 4, Diablo↑, 1, DR5↑, 1, IAP1↓, 1, iNOS↓, 2, JNK↓, 1, JNK↑, 1, MAPK↓, 2, Mcl-1↓, 3, MDM2↑, 1, p27/CDKN1B↑, 1, survivin↓, 4, Telomerase↓, 1,
Kinase & Signal Transduction(tgid=6) ⓘ
HER2/EBBR2↓, 2,
Transcription & Epigenetics(tgid=7) ⓘ
EZH2↓, 2, ac‑H3↓, 1, ac‑H3↑, 1, ac‑H4↓, 1, ac‑H4↑, 1, HATs↓, 18, miR-218↑, 1, other↑, 1, PCAF↓, 3, pRB↑, 1,
Protein Folding & ER Stress(tgid=8) ⓘ
CHOP/DDIT3↑, 2, ER Stress↑, 1, HSP70/HSPA5↓, 1, HSP90↓, 1,
Autophagy & Lysosomes(tgid=9) ⓘ
SESN2↑, 1,
DNA Damage & Repair(tgid=10) ⓘ
DFF45↓, 1, DNAdam↑, 2, DNMT1↓, 1, DNMTs↓, 4, p16↑, 1, P53↑, 2, PARP↑, 2, cl‑PARP↑, 2, PCNA↓, 2,
Cell Cycle & Senescence(tgid=11) ⓘ
CDK2↓, 3, CDK4↓, 2, CycB/CCNB1↓, 1, cycD1/CCND1↓, 4, cycE/CCNE↓, 1, P21↑, 1, TumCCA↑, 6,
Proliferation, Differentiation & Cell State(tgid=12) ⓘ
cFos↓, 1, CREB2↓, 1, CSCs↓, 2, EMT↓, 2, ERK↓, 1, FOXO↑, 1, FOXO1↓, 1, Gli1↓, 1, GSK‐3β↓, 1, HDAC↓, 6, HDAC1↓, 1, HDAC3↓, 1, HDAC8↓, 1, Let-7↑, 1, mTOR↓, 2, NOTCH↓, 1, NOTCH1↓, 2, p300↓, 6, PI3K↓, 6, Shh↓, 1, Smo↓, 1, Src↓, 1, STAT↓, 2, STAT3↓, 5, STAT5↓, 1, TumCG↓, 2, Wnt↓, 2, Wnt↑, 1, Wnt/(β-catenin)↓, 1,
Migration(tgid=13) ⓘ
5LO↓, 1, AP-1↓, 1, CDK4/6↓, 1, E-cadherin↑, 2, FAK↓, 4, Ki-67↓, 1, miR-200c↑, 1, MMP2↓, 5, MMP3↓, 1, MMP7↓, 1, MMP9↓, 7, MMPs↓, 3, N-cadherin↓, 1, PDGF↓, 1, PKA↓, 1, RECK↑, 1, SMAD2↓, 1, SMAD3↓, 1, Snail↓, 1, TGF-β↓, 2, TIMP2↑, 1, TRIB3↑, 1, TumCI↓, 5, TumCMig↓, 2, TumCP↓, 4, TumMeta↓, 6, Twist↓, 1, uPA↓, 1, Vim↓, 1, Zeb1↓, 2, ZEB2↓, 1, α-tubulin↑, 1, β-catenin/ZEB1↓, 3,
Angiogenesis & Vasculature(tgid=14) ⓘ
angioG↓, 5, EGFR↓, 2, Hif1a↓, 2, VEGF↓, 6,
Immune & Inflammatory Signaling(tgid=16) ⓘ
COX1↓, 1, COX2/PTGS2↓, 9, CXCR4↓, 1, CXCR4↑, 1, IL1↓, 1, IL18↓, 1, IL2↓, 1, IL6↓, 3, IL8↓, 1, Inflam↓, 3, IκB↑, 1, mPGES-1↓, 1, NF-kB↓, 10, PGE2↓, 2, TNF-α↓, 3,
Synaptic & Neurotransmission(tgid=18) ⓘ
AChE↓, 1, BChE↓, 1,
Hormonal & Nuclear Receptors(tgid=20) ⓘ
CDK6↓, 1,
Drug Metabolism & Resistance(tgid=21) ⓘ
BioAv↓, 1, BioAv↑, 1, BioAv↝, 2, ChemoSen↑, 4, Dose↑, 1, Dose↝, 1, eff↑, 4, Half-Life↓, 1, selectivity↑, 2,
Clinical Biomarkers(tgid=22) ⓘ
EGFR↓, 2, EZH2↓, 2, HER2/EBBR2↓, 2, IL6↓, 3, Ki-67↓, 1, NOS2↓, 1, TRIB3↑, 1,
Functional Outcomes(tgid=23) ⓘ
AntiCan↑, 4, antiNeop↑, 2, cardioP↑, 1, toxicity↓, 1,
Total Targets: 186
Pathway results for Effect on Normal Cells:
NA, unassigned(tgid=0) ⓘ
AntiArt↑, 1,
Redox & Oxidative Stress(tgid=1) ⓘ
antiOx↑, 4, Catalase↑, 1, GSTs↑, 2, HO-1↑, 1, NRF2↑, 1, ROS↓, 3, SOD↑, 1,
Core Metabolism/Glycolysis(tgid=4) ⓘ
CRM↑, 2, cytoP450↓, 1,
Transcription & Epigenetics(tgid=7) ⓘ
HATs↓, 4,
Autophagy & Lysosomes(tgid=9) ⓘ
p62↓, 1,
Proliferation, Differentiation & Cell State(tgid=12) ⓘ
EP300↓, 2, HDAC↑, 1, mTORC1↓, 1,
Migration(tgid=13) ⓘ
5LO↓, 1, AP-1↓, 1,
Angiogenesis & Vasculature(tgid=14) ⓘ
angioG↓, 1,
Immune & Inflammatory Signaling(tgid=16) ⓘ
IL1↓, 1, IL6↓, 1, Inflam↓, 4, NF-kB↓, 3, PGE2↓, 1, TNF-α↓, 1,
Synaptic & Neurotransmission(tgid=18) ⓘ
AChE↓, 1, BChE↓, 1,
Protein Aggregation(tgid=19) ⓘ
Aβ↓, 1,
Drug Metabolism & Resistance(tgid=21) ⓘ
BioAv↓, 2, BioAv↑, 2, BioAv↝, 1,
Clinical Biomarkers(tgid=22) ⓘ
IL6↓, 1,
Functional Outcomes(tgid=23) ⓘ
AntiAge↑, 1, antiPs↑, 1, cognitive↑, 1, neuroP↑, 2, radioP↑, 1, toxicity↓, 2,
Total Targets: 37
Scientific Paper Hit Count for: HATs, histone acetyltransferases
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#:886 State#:% Dir#:1
wNotes=on sortOrder:rid,rpid
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