H3 Cancer Research Results

H3, Histone 3: Click to Expand ⟱

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Type:

Histone 3 (H3) is a protein that is a component of chromatin, the complex of DNA and proteins that makes up the chromosomes in the nucleus of eukaryotic cells. H3 is one of the five main histone proteins, and it plays a crucial role in the regulation of gene expression and the maintenance of chromatin structure.
H3 has been found to be overexpressed in various types of cancer, including breast, prostate, lung, and colon cancer.

Scientific Papers found: Click to Expand⟱

5326-

ALC,

L-Carnitine Is an Endogenous HDAC Inhibitor Selectively Inhibiting Cancer Cell Growth In Vivo and In Vitro

vitro+vivo,

Liver,

HepG2

mice

TumCG↓, Here we found that (1) LC treatment selectively inhibited cancer cell growth in vivo and in vitro;
P21↑, (2) LC treatment selectively induces the expression of p21cip1 gene, mRNA and protein in cancer cells
ac‑H3↑, (4) LC increases histone acetylation and induces accumulation of acetylated histones both in normal thymocytes and cancer cells
HDAC↓, (5) LC directly inhibits HDAC I/II activities via binding to the active sites of HDAC and induces histone acetylation and lysine-acetylation accumulation in vitro;
*ATP↑, LC is able to generate ATP in normal mouse thymocytes, but not in hepatic HepG2 and SMMC-7721 cancer cells.
selectivity↑,
ac‑H4↑, LC dose-dependently increased acetylation of H3 and H4 (

177-

Api,

Inhibition of MDA-MB-231 breast cancer cell proliferation and tumor growth by apigenin through induction of G2/M arrest and histone H3 acetylation-mediated p21WAF1/CIP1 expression

in-vitro,

BC,

MDA-MB-231

Cyc↓, Cyclin A
CycB/CCNB1↓,
CDK1↓,
P21↑,
PCNA↝,
HDAC↓, apigenin treatment for 48 h suppressed HDAC activity in MDA-MB-231 cells in a dose-dependent manner
TumCP↓, Apigenin Inhibited MDA-MB-231 Cell Proliferation
TumCCA↑, Apigenin Induced G2/M Arrest in MDA-MB-231 Cells
ac‑H3↑, H3 acetylation increased in time-dependent
TumW↓, apigenin treatment significantly reduced the tumor volume and tumor weight
TumVol↓,

3160-

Ash,

Withaferin A: A Pleiotropic Anticancer Agent from the Indian Medicinal Plant Withania somnifera (L.) Dunal

Review,

Var,

TumCCA↑, withaferin A suppressed cell proliferation in prostate, ovarian, breast, gastric, leukemic, and melanoma cancer cells and osteosarcomas by stimulating the inhibition of the cell cycle at several stages, including G0/G1 [86], G2, and M phase
H3↑, via the upregulation of phosphorylated Aurora B, H3, p21, and Wee-1, and the downregulation of A2, B1, and E2 cyclins, Cdc2 (Tyr15), phosphorylated Chk1, and Chk2 in DU-145 and PC-3 prostate cancer cells.
P21↑,
cycA1/CCNA1↓,
CycB/CCNB1↓,
cycE/CCNE↓,
CDC2↓,
CHK1↓,
Chk2↓,
p38↑, nitiated cell death in the leukemia cells by increasing the expression of p38 mitogen-activated protein kinases (MAPK)
MAPK↑,
E6↓, educed the expression of human papillomavirus E6/E7 oncogenes in cervical cancer cells
E7↓,
P53↑, restored the p53 pathway causing the apoptosis of cervical cancer cells.
Akt↓, oral dose of 3–5 mg/kg withaferin A attenuated the activation of Akt and stimulated Forkhead Box-O3a (FOXO3a)-mediated prostate apoptotic response-4 (Par-4) activation,
FOXO3↑,
ROS↑, the generation of reactive oxygen species, histone H2AX phosphorylation, and mitochondrial membrane depolarization, indicating that withaferin A can cause the oxidative stress-mediated killing of oral cancer cells [
γH2AX↑,
MMP↓,
mitResp↓, withaferin A inhibited the expansion of MCF-7 and MDA-MB-231 human breast cancer cells by ROS production, owing to mitochondrial respiration inhibition
eff↑, combination treatment of withaferin A and hyperthermia induced the death of HeLa cells via a decrease in the mitochondrial transmembrane potential and the downregulation of the antiapoptotic protein myeloid-cell leukemia 1 (MCL-1)
TumCD↑,
Mcl-1↓,
ER Stress↑, . Withaferin A also attenuated the development of glioblastoma multiforme (GBM), both in vitro and in vivo, by inducing endoplasmic reticulum stress via activating the transcription factor 4-ATF3-C/EBP homologous protein (ATF4-ATF3-CHOP)
ATF4↑,
ATF3↑,
CHOP↑,
NOTCH↓, modulating the Notch-1 signaling pathway and the downregulation of Akt/NF-κB/Bcl-2 . withaferin A inhibited the Notch signaling pathway
NF-kB↓,
Bcl-2↓,
STAT3↓, Withaferin A also constitutively inhibited interleukin-6-induced phosphorylation of STAT3,
CDK1↓, lowering the levels of cyclin-dependent Cdk1, Cdc25C, and Cdc25B proteins,
β-catenin/ZEB1↓, downregulation of p-Akt expression, β-catenin, N-cadherin and epithelial to the mesenchymal transition (EMT) markers
N-cadherin↓,
EMT↓,
Cyt‑c↑, depolarization and production of ROS, which led to the release of cytochrome c into the cytosol,
eff↑, combinatorial effect of withaferin A and sulforaphane was also observed in MDA-MB-231 and MCF-7 breast cancer cells, with a dramatic reduction of the expression of the antiapoptotic protein Bcl-2 and an increase in the pro-apoptotic Bax level, thus p
CDK4↓, downregulates the levels of cyclin D1, CDK4, and pRB, and upregulates the levels of E2F mRNA and tumor suppressor p21, independently of p53
p‑RB1↓,
PARP↑, upregulation of Bax and cytochrome c, downregulation of Bcl-2, and activation of PARP, caspase-3, and caspase-9 cleavage
cl‑Casp3↑,
cl‑Casp9↑,
NRF2↑, withaferin A binding with Keap1 causes an increase in the nuclear factor erythroid 2-related factor 2 (Nrf2) protein levels, which in turn, regulates the expression of antioxidant proteins that can protect the cells from oxidative stress.
ER-α36↓, Decreased ER-α
LDHA↓, inhibited growth, LDHA activity, and apoptotic induction
lipid-P↑, induction of oxidative stress, increased lipid peroxidation,
AP-1↓, anti-inflammatory qualities of withaferin A are specifically attributed to its inhibition of pro-inflammatory molecules, α-2 macroglobulin, NF-κB, activator protein 1 (AP-1), and cyclooxygenase-2 (COX-2) inhibition,
COX2↓,
RenoP↑, showing strong evidence of the renoprotective potential of withaferin A due to its anti-inflammatory activity
PDGFR-BB↓, attenuating the BB-(PDGF-BB) platelet growth factor
SIRT3↑, by increasing the sirtuin3 (SIRT3) expression
MMP2↓, withaferin A inhibits matrix metalloproteinase-2 (MMP-2) and MMP-9,
MMP9↓,
NADPH↑, but also provokes mRNA stimulation for a set of antioxidant genes, such as NADPH quinone dehydrogenase 1 (NQO1), glutathione-disulfide reductase (GSR), Nrf2, heme oxygenase 1 (HMOX1),
NQO1↑,
GSR↑,
HO-1↑,
*SOD2↑, cardiac ischemia-reperfusion injury model. Withaferin A triggered the upregulation of superoxide dismutase SOD2, SOD3, and peroxiredoxin 1(Prdx-1).
*Prx↑,
*Casp3?, and ameliorated cardiomyocyte caspase-3 activity
eff↑, combination with doxorubicin (DOX), is also responsible for the excessive generation of ROS
Snail↓, inhibition of EMT markers, such as Snail, Slug, β-catenin, and vimentin.
Slug↓,
Vim↓,
CSCs↓, highly effective in eliminating cancer stem cells (CSC) that expressed cell surface markers, such as CD24, CD34, CD44, CD117, and Oct4 while downregulating Notch1, Hes1, and Hey1 genes;
HEY1↓,
MMPs↓, downregulate the expression of MMPs and VEGF, as well as reduce vimentin, N-cadherin cytoskeleton proteins,
VEGF↓,
uPA↓, and protease u-PA involved in the cancer cell metastasis
*toxicity↓, A was orally administered to Wistar rats at a dose of 2000 mg/kg/day and had no adverse effects on the animals
CDK2↓, downregulated the activation of Bcl-2, CDK2, and cyclin D1
CDK4↓, Another study also demonstrated the inhibition of Hsp90 by withaferin A in a pancreatic cancer cell line through the degradation of Akt, cyclin-dependent kinase 4 Cdk4,
HSP90↓,

4981-

ATV,

Crosstalk between Statins and Cancer Prevention and Therapy: An Update

Apoptosis↑, The anti-tumor activity of statins is largely related to their ability to induce apoptosis by targeting cancer cells with high selectivity.
selectivity↑,
eff↑, Combining statins with histone deacetylase inhibitors can induce a synergistic anticancer effect.
HMG-CoA↓, 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, known as statins, are a commonly used and well-tolerated class of drugs used in lipid disorders,
*cardioP↑, Their effectiveness in preventing the development of cardiovascular diseases makes statins one of the most widely used drugs
OS↑, On the other hand, improved survival in patients with hepatocellular carcinoma, colon cancer or prostate cancer is visible after the use of any statin
IL1β↓, statins inhibit the synthesis of cytokines, including interleukin (IL-) IL-1β, IL-6, IL-8 and tumor necrosis factor alpha (TNF-α)
IL6↓,
IL8↓,
TNF-α↓,
TumAuto↑, Simvastatin-induced autophagy has been reported in rhabdomyosarcoma cells [
Histones↝, Statins are also involved in the regulation of the histone acetylation level.
ac‑H3↑, Studies indicate that statins increase histone H3 and H4 acetylation as well as inhibit class I and II HDACs
ac‑H4↑,
HDAC↓,

2699-

BBR,

Plant Isoquinoline Alkaloid Berberine Exhibits Chromatin Remodeling by Modulation of Histone Deacetylase To Induce Growth Arrest and Apoptosis in the A549 Cell Line

in-vitro,

Lung,

A549

HDAC↓, BBR represses total HDAC and also class I, II, and IV HDAC activity through hyperacetylation of histones.
TumCCA↑, BBR triggers positive regulation of the sub-G0/G1 cell cycle progression phase in A549 cells.
TNF-α↓, BBR downregulates oncogenes (TNF-α, COX-2, MMP-2, and MMP-9) and upregulates tumor suppressor genes (p21 and p53) mRNA and protein expressions.
COX2↓,
MMP2↓, BBR Induces Downregulation of MMP-2 and MMP-9
MMP9↓,
P21↑,
P53↑,
Casp↑, triggered the caspase cascade apoptotic pathway in A549 cells
ac‑H3↑, BBR Increases the Acetylation State of Histones H3 and H4.
ac‑H4↑,
ROS↑, BBR Induces ROS Generation, Δψm Alteration, Membrane Loss, and Nuclear Fragmentation
MMP↓,

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

5227-

EMD,

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

vitro+vivo,

Nor,

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

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

798-

GAR,

Garcinol, an acetyltransferase inhibitor, suppresses proliferation of breast cancer cell line MCF-7 promoted by 17β-estradiol

in-vitro,

BC,

MCF-7

TumCP↓,
TumCCA↑, arrested at G0/G1 phase
Apoptosis↑,
ac‑H3↑,
ac‑H4∅, not inhibited by garcinol
NF-kB↓,
ac‑p65↑,
cycD1/CCND1↓,
Bcl-2↓,
Bcl-xL↓,

1504-

GEN,

Epigenetic targets of bioactive dietary components for cancer prevention and therapy

Review,

NA,

DNMTs↓, genistein has DNA methyltransferase inhibitory activity
P21↑,
p16↑,
ac‑H3↑, genistein increased acetylated histones 3 and 4
ac‑H4↑,
TumCCA↑,
Casp↑,
Apoptosis↑,
hTERT/TERT↓, also inhibits the expression of tumor promoter genes such as hTERT
BTG3↑, reactivates BTG3, a tumor suppressor gene, in A498, ACHN, and HEK-293 renal carcinoma cell lines

2875-

HNK,

Inhibition of class I histone deacetylases in non-small cell lung cancer by honokiol leads to suppression of cancer cell growth and induction of cell death in vitro and in vivo

in-vitro,

Lung,

A549

20, 40 and 60 µM

in-vitro,

Lung,

H1299

in-vitro,

Lung,

H460

in-vitro,

SCC,

H226

HDAC↓, Treatment of NSCLC cells (A549, H1299, H460 and H226) with honokiol (20, 40 and 60 µM) inhibited histone deacetylase (HDAC) activity, reduced the levels of class I HDAC proteins and enhanced histone acetyltransferase activity in a dose-dependent man
tumCV↓, These effects of honokiol were associated with a significant reduction in the viability of NSCLC cells
TumCCA↑, Treatment of A549 and H1299 cells with honokiol resulted in an increase in G1 phase arrest, and a decrease in the levels of cyclin D1, D2 and cyclin dependent kinases.
cycD1/CCND1↓,
ac‑H3↑, Honokiol increases the levels of acetylated histone H3 and H4 in NSCLC cells
ac‑H4↑,
selectivity↑, Honokiol inhibits cell growth or viability of human NSCLC cells but not normal human bronchial epithelial cells
CDK2↓, Similarly, a marked reduction in the expression of CDK2, CDK4 and CDK6 proteins was observed
CDK4↓,

2864-

HNK,

Honokiol: A Review of Its Anticancer Potential and Mechanisms

Review,

Var,

TumCCA↑, induction of G0/G1 and G2/M cell cycle arrest
CDK2↓, (via the regulation of cyclin-dependent kinase (CDK) and cyclin proteins),
EMT↓, epithelial–mesenchymal transition inhibition via the downregulation of mesenchymal markers
MMPs↓, honokiol possesses the capability to supress cell migration and invasion via the downregulation of several matrix-metalloproteinases
AMPK↑, (activation of 5′ AMP-activated protein kinase (AMPK) and KISS1/KISS1R signalling)
TumCI↓, inhibiting cell migration, invasion, and metastasis, as well as inducing anti-angiogenesis activity (via the down-regulation of vascular endothelial growth factor (VEGFR) and vascular endothelial growth factor (VEGF)
TumCMig↓,
TumMeta↓,
VEGFR2↓,
*antiOx↑, diverse biological activities, including anti-arrhythmic, anti-inflammatory, anti-oxidative, anti-depressant, anti-thrombocytic, and anxiolytic activities
*Inflam↓,
*BBB↑, Due to its ability to cross the blood–brain barrier
*neuroP↑, beneficial towards neuronal protection through various mechanism, such as the preservation of Na+/K+ ATPase, phosphorylation of pro-survival factors, preservation of mitochondria, prevention of glucose, reactive oxgen species (ROS), and inflammatory
*ROS↓,
Dose↝, Generally, the concentrations used for the in vitro studies are between 0–150 μM
selectivity↑, Interestingly, honokiol has been shown to exhibit minimal cytotoxicity against on normal cell lines, including human fibroblast FB-1, FB-2, Hs68, and NIH-3T3 cells
Casp3↑, ↑ Caspase-3 & caspase-9
Casp9↑,
NOTCH1↓, Inhibition of Notch signalling: ↓ Notch1 & Jagged-1;
cycD1/CCND1↓, ↓ cyclin D1 & c-Myc;
cMyc↓,
P21?, ↑ p21WAF1 protein
DR5↑, ↑ DR5 & cleaved PARP
cl‑PARP↑,
P53↑, ↑ phosphorylated p53 & p53
Mcl-1↑, ↓ Mcl-1 protein
p65↓, ↓ p65; ↓ NF-κB
NF-kB↓,
ROS↑, ↑ JNK activation ,Increase ROS activity:
JNK↑,
NRF2↑, ↑ Nrf2 & c-Jun protein activation
cJun↑,
EF-1α↓, ↓ EFGR; ↓ MAPK/PI3K pathway activity
MAPK↓,
PI3K↓,
mTORC1↓, ↓ mTORC1 function; ↑ LKB1 & cytosolic localisation
CSCs↓, Inhibit stem-like characteristics: ↓ Oct4, Nanog & Sox4 protein; ↓ STAT3;
OCT4↓,
Nanog↓,
SOX4↓,
STAT3↓,
CDK4↓, ↓ Cdk2, Cdk4 & p-pRbSer780;
p‑RB1↓,
PGE2↓, ↓ PGE2 production ↓ COX-2 ↑ β-catenin
COX2↓,
β-catenin/ZEB1↑,
IKKα↓, ↓ IKKα
HDAC↓, ↓ class I HDAC proteins; ↓ HDAC activity;
HATs↑, ↑ histone acetyltransferase (HAT) activity; ↑ histone H3 & H4
H3↑,
H4↑,
LC3II↑, ↑ LC3-II
c-Raf↓, ↓ c-RAF
SIRT3↑, ↑ Sirt3 mRNA & protein; ↓ Hif-1α protein
Hif1a↓,
ER Stress↑, ↑ ER stress signalling pathway activation; ↑ GRP78,
GRP78/BiP↑,
cl‑CHOP↑, ↑ cleaved caspase-9 & CHOP;
MMP↓, mitochondrial depolarization
PCNA↓, ↓ cyclin B1, cyclin D1, cyclin D2 & PCNA;
Zeb1↓, ↓ ZEB2 Inhibit
NOTCH3↓, ↓ Notch3/Hes1 pathway
CD133↓, ↓ CD133 & Nestin protein
Nestin↓,
ATG5↑, ↑ Atg7 protein activation; ↑ Atg5;
ATG7↑,
survivin↓, ↓ Mcl-1 & survivin protein
ChemoSen↑, honokiol potentiated the apoptotic effect of both doxorubicin and paclitaxel against human liver cancer HepG2 cells.
SOX2↓, Honokiol was shown to downregulate the expression of Oct4, Nanog, and Sox2 which were known to be expressed in osteosarcoma, breast carcinoma and germ cell tumours
OS↑, Lipo-HNK was also shown to prolong survival and induce intra-tumoral apoptosis in vivo.
P-gp↓, Honokiol was shown to downregulate the expression of P-gp at mRNA and protein levels in MCF-7/ADR, a human breast MDR cancer cell line
Half-Life↓, For i.v. administration, it has been found that there was a rapid rate of distribution followed by a slower rate of elimination (elimination half-life t1/2 = 49.22 min and 56.2 min for 5 mg or 10 mg of honokiol, respectively
Half-Life↝, male and female dogs was assessed. The elimination half-life (t1/2 in hours) was found to be 20.13 (female), 9.27 (female), 7.06 (male), 4.70 (male), and 1.89 (male) after administration of doses of 8.8, 19.8, 3.9, 44.4, and 66.7 mg/kg, respectively.
eff↑, Apart from that, epigallocatechin-3-gallate functionalized chitin loaded with honokiol nanoparticles (CE-HK NP), developed by Tang et al. [224], inhibit HepG2
BioAv↓, extensive biotransformation of honokiol may contribute to its low bioavailability.

2049-

PB,

Modifying histones to tame cancer: clinical development of sodium phenylbutyrate and other histone deacetylase inhibitors

Review,

Var,

HDAC↓, TOf the butyric acid derivatives, sodium phenylbutyrate has undergone the most extensive systematic investigation
ac‑H3↑, The accumulation of multi-acetylated forms of histones H3 and H4 in cultured cells exposed to millimolar concentrations of sodium butyrate was originally reported in 1978
ac‑H4↑,
ac‑H3↑, Like the parental compound, sodium phenylbutyrate leads to induction of histone acetylation in erythroleu kaemia cells [23] and myeloid leukaemia cells
eff↝, In erythroleukaemia cells, butyrate was a stronger inhibitor of histone deacetylase than PB or phenylacetate (PA), which were stronger HDAC inhibitors than butyramide and isobutyramide
toxicity↓, Preliminary data from the Phase I trials suggest that PB can be safely administered for prolonged periods of time, through both iv. and oral routes.

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

3368-

QC,

The potential anti-cancer effects of quercetin on blood, prostate and lung cancers: An update

Review,

Var,

*Inflam↓, quercetin is known for its anti-inflammatory, antioxidant, and anticancer properties.
*antiOx↑,
*AntiCan↑,
Casp3↓, Quercetin increases apoptosis and autophagy in cancer by activating caspase-3, inhibiting the phosphorylation of Akt, mTOR, and ERK, lessening β-catenin, and stabilizing the stabilization of HIF-1α.
p‑Akt↓,
p‑mTOR↓,
p‑ERK↓,
β-catenin/ZEB1↓,
Hif1a↓,
AntiAg↓, Quercetin have revealed an anti-tumor effect by reducing development of blood vessels. I
VEGFR2↓, decrease tumor growth through targeting VEGFR-2-mediated angiogenesis pathway and suppressing the downstream regulatory component AKT in prostate and breast malignancies.
EMT↓, effects of quercetin on inhibition of EMT, angiogenesis, and invasiveness through the epidermal growth factor receptor (EGFR)/VEGFR-2-mediated pathway in breast cancer
EGFR↓,
MMP2↓, MMP2 and MMP9 are two remarkable compounds in metastatic breast cancer (28–30). quercetin on breast cancer cell lines (MDA-MB-231) and showed that after treatment with this flavonoid, the expression of these two proteinases decreased
MMP↓,
TumMeta↓, head and neck (HNSCC), the inhibitory effect of quercetin on the migration of tumor cells has been shown by regulating the expression of MMPs
MMPs↓,
Akt↓, quercetin by inhibiting the Akt activation pathway dependent on Snail, diminishing the expression of N-cadherin, vimentin, and ADAM9 and raising the expression of E-cadherin and proteins
Snail↓,
N-cadherin↓,
Vim↓,
E-cadherin↑,
STAT3↓, inhibiting STAT3 signaling
TGF-β↓, reducing the expression of TGF-β caused by vimentin and N-cadherin, Twist, Snail, and Slug and increasing the expression of E-cadherin in PC-3 cells.
ROS↓, quercetin exerted an anti-proliferative role on HCC cells by lessening intracellular ROS independently of p53 expression
P53↑, increasing the expression of p53 and BAX in hepatocellular carcinoma (HepG2) cell lines through the reduction of PKC, PI3K, and cyclooxygenase (COX-2)
BAX↑,
PKCδ↓,
PI3K↓,
COX2↓,
cFLIP↓, quercetin by inhibiting PI3K/AKT/mTOR and STAT3 pathways, decreasing the expression of cellular proteins such as c-FLIP, cyclin D1, and c-Myc, as well as reducing the production of IL-6 and IL-10 cytokines, leads to the death of PEL cells
cycD1/CCND1↓,
cMyc↓,
IL6↓,
IL10↓,
Cyt‑c↑, In addition, quercetin induced c-cytochrome-dependent apoptosis and caspase-3 almost exclusively in the HSB2 cell line
TumCCA↑, Exposure of K562 cells to quercetin also significantly raised the cells in the G2/M phase, which reached a maximum peak in 24 hours
DNMTs↓, pathway through DNA demethylation activity, histone deacetylase (HDAC) repression, and H3ac and H4ac enrichment
HDAC↓,
ac‑H3↑,
ac‑H4↑,
Diablo↑, SMAC/DIABLO exhibited activation
Casp3↑, enhanced levels of activated caspase 3, cleaved caspase 9, and PARP1
Casp9↑,
PARP1↑,
eff↑, green tea and quercetin as monotherapy caused the reduction of levels of anti-apoptotic proteins, CDK6, CDK2, CYCLIN D/E/A, BCL-2, BCL-XL, and MCL-1 and an increase in expression of BAX.
PTEN↑, Quercetin upregulates the level of PTEN as a tumor suppressor, which inhibits AKT signaling
VEGF↓, Quercetin had anti-inflammatory and anti-angiogenesis effects, decreasing VGEF-A, NO, iNOS, and COX-2 levels
NO↓,
iNOS↓,
ChemoSen↑, quercetin and chemotherapy can potentiate their effect on the malignant cell
eff↑, combination with hyperthermia, Shen et al. Quercetin is a method used in cancer treatment by heating, and it was found to reduce Doxorubicin hydrochloride resistance in leukemia cell line K562
eff↑, treatment with ellagic acid, luteolin, and curcumin alone showed excellent anticancer effects.
eff↑, co-treatment with quercetin and curcumin led to a reduction of mitochondrial membrane integrity, promotion of cytochrome C release, and apoptosis induction in CML cells
uPA↓, A-549 cells were shown to have reduced mRNA expressions of urokinase plasminogen activator (uPA), Upar, protein expression of CXCR-4, CXCL-12, SDF-1 when quercetin was applied at 20 and 40 mM/ml by real-time PCR.
CXCR4↓,
CXCL12↓,
CLDN2↓, A-549 cells, indicated that quercetin could reduce mRNA and protein expression of Claudin-2 in A-549 cell lines without involving Akt and ERK1/2,
CDK6↓, CDK6, which supports the growth and viability of various cancer cells, was hampered by the dose-dependent manner of quercetin (IC50 dose of QR for A-549 cells is 52.35 ± 2.44 μM).
MMP9↓, quercetin up-regulated the rates of G1 phase cell cycle and cellular apoptotic in both examined cell lines compared with the control group, while it declined the expressions of the PI3K, AKT, MMP-2, and MMP-9 proteins
TSP-1↑, quercetin increased TSP-1 mRNA and protein expression to inhibit angiogenesis,
Ki-67↓, significant reductions in Ki67 and PCNA proliferation markers and cell survival markers in response to quercetin and/or resveratrol.
PCNA↓,
ROS↑, Also, quercetin effectively causes intracellular ROS production and ER stress
ER Stress↑,

4198-

SFN,

Sulforaphane epigenetically enhances neuronal BDNF expression and TrkB signaling pathways

vitro+vivo,

AD,

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

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

3661-

SFN,

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

in-vitro,

AD,

mice

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

1725-

SFN,

Anticancer Activity of Sulforaphane: The Epigenetic Mechanisms and the Nrf2 Signaling Pathway

Review,

Var,

*toxicity∅, Sulforaphane (SFN), a compound derived from cruciferous vegetables that has been shown to be safe and nontoxic, with minimal/no side effects
AntiCan↑, such as anticancer and antioxidant activities.
antiOx↑,
NRF2↑, FN also upregulates a series of cytoprotective genes by activating nuclear factor erythroid-2- (NF-E2-) related factor 2 (Nrf2), a critical transcription factor activated in response to oxidative stress;
DNMTs↓, SFN can reverse such epigenetic alterations in cancers by targeting DNA methyltransferases (DNMTs), histone deacetyltransferases (HDACs)
HDAC↓,
Hif1a↓, By suppressing the expression and activity of hypoxia inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF), SFN inhibited the angiogenesis and metastasis of ovarian and colon cancers
VEGF↓,
P21↑, 15 μM SFN treatment caused reexpression of p21WAF1/CIP1 due to reduced expression of class I and II HDACs
TumCCA↑, resulted in cell cycle arrest
ac‑H3↑, upregulation of acetylated histone H3 and H4
ac‑H4↑,
DNAdam↑, SFN induced DNA damage
Dose↝, To achieve the effective inhibition of HDAC activity, it was reported that the concentration of SFN used in vitro experiments was from 3 to 15 μM, a single oral dose of 10 μmol in mice, and 68 g broccoli sprouts in human

1471-

SFN,

ROS-mediated activation of AMPK plays a critical role in sulforaphane-induced apoptosis and mitotic arrest in AGS human gastric cancer cells

in-vitro,

GC,

AGS

TumCP↓,
Apoptosis↑,
TumCCA↑, G2/M phase
CycB/CCNB1↑,
P21↑,
p‑H3↑,
p‑AMPK↑,
eff↓, compound C, an AMPK inhibitor, significantly blocked sulforaphane-induced apoptosis
MMP↓,
Cyt‑c↑,
ROS↑, sulforaphane provoked the generation of intracellular ROS
eff↓, sulforaphane provoked the generation of intracellular ROS; especially when ROS production was blocked by antioxidant N-acetylcysteine, both AMPK activation and growth inhibition by sulforaphane were completely abolished

1453-

SFN,

Sulforaphane Reduces Prostate Cancer Cell Growth and Proliferation In Vitro by Modulating the Cdk-Cyclin Axis and Expression of the CD44 Variants 4, 5, and 7

in-vitro,

Pca,

DU145

1–20 µM

14-32uM

Other investigators have calculated the IC50 value for SFN to be 14 µM for DU145 versus 32 µM for PC3

in-vitro,

Pca,

PC3

TumCG↓,
TumCP↓,
TumCCA↑, cell cycle arrest at the S- and G2/M-phase
H3↑,
H4↑,
HDAC↓, SFN acts as a histone deacetylase (HDAC) inhibitor.
CDK1↑, With 10 µM SFN, CDK1 and CDK2 increased in both cell lines,
CDK2↑,
p19↑,
*BioAv↑, A transient decrease in HDAC activity has also been observed in healthy humans 3 h after providing a daily 200 µM SFN dose, resulting in a plasma concentration of SFN metabolites of 0.1–0.2 µM

1434-

SFN,

GEM,

Sulforaphane Potentiates Gemcitabine-Mediated Anti-Cancer Effects against Intrahepatic Cholangiocarcinoma by Inhibiting HDAC Activity

in-vitro,

CCA,

HuCCT1

 SFN (0–80 μM) or GEM (0–10 μM) for 24 h

27.4uM(SFN),0.57 μM(GEM)

in-vitro,

CCA,

HuH28

34.2 μM(SFN), 0.71um(GEM)

in-vivo,

NA,

50 mg/kg/day

tumors of SFN- and GEM-treated mice

HDAC↓,
ac‑H3↑,
ChemoSen↑, SFN synergistically augmented the GEM-mediated attenuation of cell viability and proliferation
tumCV↓,
TumCP↓,
TumCCA↑, G2/M cell cycle arrest
Apoptosis↑,
cl‑Casp3↑,
TumCI↓,
VEGF↓, VEGFA
VEGFR2↓,
Hif1a↓,
eNOS↓,
EMT?, SFN effectively inhibited the GEM-mediated induction of epithelial–mesenchymal transition (EMT)
TumCG↓,
Ki-67↓,
TUNEL↑, increased TUNEL+ apoptotic cells
P21↑,
p‑Chk2↑,
CDC25↓, decreased p-Cdc25C
BAX↑,
*ROS↓, SFN is also known to exert anti-oxidative effects via Nrf2 activation. in vivo study, optimization is performed by evaluating the anti-oxidative property of SFN in the liver.
NQO1?, identified 50 mg/kg/day as the minimal dose that significantly induced these anti-oxidative genes

1497-

SFN,

Differential effects of sulforaphane on histone deacetylases, cell cycle arrest and apoptosis in normal prostate cells versus hyperplastic and cancerous prostate cells

in-vitro,

Nor,

PrEC

in-vitro,

Pca,

LNCaP

15 µM SFN

in-vitro,

Pca,

PC3

HDAC↓, ability of SFN to inhibit histone deacetylase enzymes
selectivity↑, 15 µM SFN selectively induced cell cycle arrest and apoptosis in BPH1, LnCap and PC3 cells but not PrEC cells
TumCCA↑,
Apoptosis↑,
selectivity↑, selectively decreased HDAC activity
H3↑,
P21↑, in prostate cancer cells
selectivity↑, we conclude that SFN exerts differential effects on cell proliferation, HDAC activity and downstream targets in normal and cancer cells.

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:

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

antiOx↑, 2, Prx↑, 1, ROS↓, 2, SOD2↑, 1,

Mitochondria & Bioenergetics ⓘ

ATP↑, 1,

Core Metabolism/Glycolysis ⓘ

CREB↑, 1,

Cell Death ⓘ

Casp3?, 1,

Transcription & Epigenetics ⓘ

H3↑, 1, ac‑H3↑, 1, H4↑, 1, ac‑H4↑, 1,

Proliferation, Differentiation & Cell State ⓘ

ERK↑, 1, HDAC↓, 1, HDAC1↓, 1, HDAC2↓, 2, HDAC3↓, 1,

Barriers & Transport ⓘ

BBB↑, 2,

Immune & Inflammatory Signaling ⓘ

Inflam↓, 2,

Synaptic & Neurotransmission ⓘ

BDNF↑, 1, TrkB↑, 1,

Protein Aggregation ⓘ

Aβ↓, 1,

Drug Metabolism & Resistance ⓘ

BioAv↑, 2,

Functional Outcomes ⓘ

AntiCan↑, 1, cardioP↑, 2, cognitive↑, 1, neuroP↑, 2, toxicity↓, 1, toxicity∅, 1,
Total Targets: 28

Scientific Paper Hit Count for: H3, Histone 3

7 Sulforaphane (mainly Broccoli)
2 EGCG (Epigallocatechin Gallate)
2 Honokiol
2 Quercetin
1 Acetyl-l-carnitine
1 Apigenin (mainly Parsley)
1 Ashwagandha(Withaferin A)
1 Atorvastatin
1 Berberine
1 Butyrate
1 Emodin
1 Garcinol
1 Genistein (soy isoflavone)
1 Phenylbutyrate
1 Gemcitabine (Gemzar)

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#:890  State#:%  Dir#:2
  wNotes=on  sortOrder:rid,rpid

H3 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 ⓘ

Mitochondria & Bioenergetics ⓘ

Core Metabolism/Glycolysis ⓘ

Cell Death ⓘ

Transcription & Epigenetics ⓘ

Proliferation, Differentiation & Cell State ⓘ

Barriers & Transport ⓘ

Immune & Inflammatory Signaling ⓘ

Synaptic & Neurotransmission ⓘ

Protein Aggregation ⓘ

Drug Metabolism & Resistance ⓘ

Functional Outcomes ⓘ

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