HDAC Cancer Research Results

HDAC, Histone deacetylases: Click to Expand ⟱

Source:

Type:

Enzymes involved in regulating gene expression by removing acetyl groups from histones, the proteins around which DNA is wrapped.
-Many cancers exhibit altered expression levels of HDACs, which can contribute to the dysregulation of genes involved in cell growth, survival, and differentiation.
-HDACs can repress the expression of tumor suppressor genes, leading to uncontrolled cell proliferation and survival. This repression can be a key factor in the development and progression of cancer.
-HDAC inhibitors (HDACi) have been developed and are being investigated for their ability to reactivate silenced genes, induce cell cycle arrest, and promote apoptosis in cancer cells.
-HDAC1, HDAC2): Often overexpressed in various cancers, including breast, prostate, and colorectal cancers. Their overexpression is associated with poor prognosis.
-HDAC4, HDAC5): These may have both oncogenic and tumor-suppressive roles depending on the context and cancer type.
-While HDACs are not classified as traditional oncogenes, their overexpression and activity can contribute to oncogenic processes.
-HDAC inhibitor works by preventing the removal of acetyl groups from histones, thereby modulating gene expression, influencing cell behavior, and potentially reversing aberrant gene silencing seen in various diseases.
-HDAC inhibitors can help reactivate these genes, thereby inhibiting growth and inducing apoptosis in cancer cells.

Scientific Papers found: Click to Expand⟱

5271-

3BP,

The anticancer agent 3-bromopyruvate: a simple but powerful molecule taken from the lab to the bedside

Review,

Var,

selectivity↑, 3-bromopyruvate (3BP), a simple alkylating chemical compound was presented to the scientific community as a potent anticancer agent, able to cause rapid toxicity to cancer cells without bystander effects on normal tissues.
selectivity↑, results obtained in cancer research with this small molecule have contradicted the just noted general fear. Indeed, a promising drug has been revealed with an effective mechanism of action and an outstanding selectivity towards cancer cells
ATP↓, once inside cancer cells 3BP can then inhibit both of their energy (ATP) producing systems, i.e., glycolysis, likely by inhibiting hexokinase-2 (hk-2) and mitochondrial oxidative phosphorylation
Glycolysis↓,
HK2↓,
mt-OXPHOS↓,
GAPDH↓, Different reports have shown that 3BP is able to inhibit GAPDH activity leading to the loss of the ATP-producing steps that occur downstream of this enzyme
mtDam↑, Mitochondria related cell death has also been reported following 3BP treatment.
GSH↓, Ehrke and co-workers have demonstrated that 3BP inhibits glycolysis and deplete the glutathione levels in primary rat astrocytes
ROS↑, Others have also observed an increase in ROS levels following 3BP treatment that induces endoplasmic reticulum stress
ER Stress↑,
TumAuto↑, Autophagy has been associated with 3BP activity in breast cancer cell lines (Zhang et al., 2014),
LC3‑Ⅱ/LC3‑Ⅰ↑, 3BP leads to aggressive autophagy involving a decrease in the ratio of LC3I/LC3II and the levels of p62 as well as dephosphorylation of Akt and p53.
p62↓,
Akt↓,
HDAC↓, 3BP’s, it has been reported to be involved in suppressing epigenetic events as it inhibits histone deacetylase (HDAC) isoforms 1 and 3 in MCF-7 breast cancer cells leading to apoptosis
TumCA↑, Proliferation inhibition by 3BP treatment has also been related with the induction of S-phase and G2/M- phase arrest (Liu et al. 2009)
Bcl-2↓, downregulation of the expression of Bcl-2, c-Myc and mutant p53, the upregulation of Bax, activation of caspase-3 and mitochondrial leakage of cytochrome c
cMyc↓,
Casp3↑,
Cyt‑c↑,
Mcl-1↓, mitochondria mediated apoptosis triggered by 3BP was found to be associated with the downregulation of Mcl-1 through the phosphoinositide-3-kinase/Akt pathway (Liu et al. 2014).
PARP↓, 3BP treatment decreases the levels of poly(ADP-ribose) polymerase (PARP) and cleaved PARP.
ChemoSen↑, it might be a good adjuvant for commonly used chemotherapy agents, or a replacement for such agents.

2663-

AL,

Therapeutic Effect of Allicin on Glioblastoma

in-vitro,

GBM,

U251

in-vitro,

GBM,

U87MG

BioAv↝, After processing, such as cutting, crushing, chewing, or dehydration, alliinase rapidly breaks down alliin to form allicin. Allicin is immediately decomposed to other organosulfur compounds such as diallyl sulphide (DAS), diallyl disulfide(DADS), and
TumCCA↑, The results show DATS can reduce tumor growth by inhibits cell cycle progression and promotes p53-mediated tumor suppression pathways
P53↑,
HDAC↓, The findings demonstrate that DATS can inhibit U87MG cell growth in vivo by inhibiting HDAC [10].
CSCs↓, Inhibition of cancer stem cells(CSC)
ROS↑, DATS can induce apoptosis by ROS through regulation of Bcl-2 and have anticancer effect on human glioblastoma (U87MG) and neuroblastoma (SH-SY5Y) cells
ChemoSen↑, The most interesting thing is allicin can enhance the sensitivity of TMZ-resistant cells to TMZ by inhibiting MGMT expression.
MGMT↓,

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 (

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.

1156-

And,

Exploring the potential of Andrographis paniculata for developing novel HDAC inhibitors: an in silico approach

Analysis,

NA,

HDAC↓, Andrographidine E had the highest binding affinities towards HDAC1

1151-

Api,

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

in-vitro,

Pca,

PC3

20–40μM

in-vitro,

Pca,

22Rv1

in-vivo,

NA,

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

mouse

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

1547-

Api,

Apigenin: Molecular Mechanisms and Therapeutic Potential against Cancer Spreading

Review,

NA,

angioG↓,
EMT↓,
CSCs↓,
TumCCA↑,
Dose∅, Dried parsley 45,035ug/g: Dried chamomille flower 3000–5000ug/g: Parsley 2154.6ug/g:
ROS↑, activity of Apigenin has been linked to the induction of oxidative stress in cancer cells
MMP↓, triggering intracellular ROS accumulation and loss of mitochondrial integrity
Catalase↓, catalase and glutathione (GSH), molecules involved in alleviating oxidative stress, were downregulated after Apigenin
GSH↓,
PI3K↓, suppression of the PI3K/Akt and NF-κB
Akt↓,
NF-kB↓,
OCT4↓, glycosylated form of Apigenin (i.e., Vitexin) was able to suppress stemness features of human endometrial cancer, as documented by the downregulation of Oct4 and Nanog
Nanog↓,
SIRT3↓, inhibition of sirtuin-3 (SIRT3) and sirtuin-6 (SIRT6) protein levels
SIRT6↓,
eff↑, ability of Apigenin to interfere with CSC features is often enhanced by the co-administration of other flavonoids, such as chrysin
eff↑, Apigenin combined with a chemotherapy agent, temozolomide (TMZ), was used on glioblastoma cells and showed better performance in cell arrest at the G2 phase compared with Apigenin or TMZ alone,
Cyt‑c↑, release of cytochrome c (Cyt c)
Bax:Bcl2↑, Apigenin has been shown to induce the apoptosis death pathway by increasing the Bax/Bcl-2 ratio
p‑GSK‐3β↓, Apigenin has been shown to prevent activation of phosphorylation of glycogen synthase kinase-3 beta (GSK-3β)
FOXO3↑, Apigenin administration increased the expression of forkhead box O3 (FOXO3)
p‑STAT3↓, Apigenin can induce apoptosis via inhibition of STAT3 phosphorylation
MMP2↓, downregulation of the expression of MMP-2 and MMP-9
MMP9↓,
COX2↓, downregulation of PI3K/Akt in leukemia HL60 cells [156,157] and of COX2, iNOS, and reactive oxygen species (ROS) accumulation in breast cancer cells
MMPs↓, triggering intracellular ROS accumulation and loss of mitochondrial integrity, as proved by low MMP in Apigenin-treated cells
NRF2↓, suppressed the nuclear factor erythroid 2-related factor 2 (Nrf2)
HDAC↓, inhibition of histone deacetylases (HDACs) is the mechanism through which Apigenin induces apoptosis in prostate cancer cells
Telomerase↓, Apigenin has been shown to downregulate telomerase activity
eff↑, Indeed, co-administration with 5-fluorouracil (5-FU) increased the efficacy of Apigenin in human colon cancer through p53 upregulation and ROS accumulation
eff↑, Apigenin synergistically enhances the cytotoxic effects of Sorafenib
eff↑, pretreatment of pancreatic BxPC-3 cells for 24 h with a low concentration of Apigenin and gemcitabine caused the inhibition of the GSK-3β/NF-κB signaling pathway, leading to the induction of apoptosis
eff↑, In NSCLC cells, compared to monotherapy, co-treatment with Apigenin and naringenin increased the apoptotic rate through ROS accumulation, Bax/Bcl-2 increase, caspase-3 activation, and mitochondrial dysfunction
eff↑, Several studies have shown that Apigenin-induced autophagy may play a pro-survival role in cancer therapy; in fact, inhibition of autophagy has been shown to exacerbate the toxicity of Apigenin
XIAP↓,
survivin↓,
CK2↓,
HSP90↓,
Hif1a↓,
FAK↓,
EMT↓,

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.

2631-

Api,

Apigenin Induces Autophagy and Cell Death by Targeting EZH2 under Hypoxia Conditions in Gastric Cancer Cells

in-vivo,

GC,

mice

in-vitro,

GC,

AGS

ER Stress↑, We further show that APG induces ER stress- and autophagy-related cell death through the inhibition of HIF-1α and Ezh2 under normoxia and hypoxia.
Hif1a↓, APG Inhibits HIF-1α and Induces Cell Death under Hypoxia in GC Cells
EZH2↓,
HDAC↓, Apigenin, a flavonoid found in traditional medicine, fruits, and vegetables and an HDAC inhibitor, is a powerful anti-cancer agent against various cancer cell lines.
TumAuto↑, APG Induces Autophagic Cell Death in GC Cells
p‑mTOR↓, APG decreased the phosphorylation of mTOR and increased the activation of AMPKα and ULK1
AMPKα↑,
GRP78/BiP↑, APG mediates the up-regulation of GRP78 through exosomes, and that this effect causes ER stress-induced cell death in APG-treated GC cells.
ROS↑, APG generates intracellular ROS release in colorectal cancer cells, and it causes various cell death types, including cell cycle arrest, chromatin condensation, MMP loss, intracellular Ca2+, annexin-v-positive cells, and ER stress-related cell death
MMP↓,
Ca+2↑, we found that APG exerts intracellular Ca2+ release in a dose- and time-dependent manner
ATF4↑, APG also increased ATF4 and CHOP in a time-dependent manner
CHOP↑,

2639-

Api,

Plant flavone apigenin: An emerging anticancer agent

Review,

Var,

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

2664-

Api,

Progress in discovery and development of natural inhibitors of histone deacetylases (HDACs) as anti-cancer agents

Review,

Var,

HDAC↓, Inhibition of HDAC by apigenin results in H3 and H4 acetylation and hyperacetylation of H3 on the p21/waf1 promoter region.

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↓,

3175-

Ash,

SFN,

Withaferin A and sulforaphane regulate breast cancer cell cycle progression through epigenetic mechanisms

in-vitro,

BC,

MDA-MB-231

in-vitro,

BC,

MCF-7

DNMTs↓, Withaferin A (WA), found in the Indian winter cherry and documented as a DNA methyl transferase (DNMT) inhibitor,
HDAC↓, sulforaphane (SFN), a well-known histone deacetylase (HDAC) inhibitor
eff↑, SFN + WA synergistically promote breast cancer cell death

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

5449-

ATV,

Pleiotropic effects of statins: A focus on cancer

NA,

Var,

lipid-P↓, Statins exhibit “pleiotropic” properties that are independent of their lipid-lowering effects.
TumCG↓, preclinical evidence suggests that statins inhibit tumor growth and induce apoptosis in specific cancer cell types.
Apoptosis↑,
ChemoSen↑, statins show chemo-sensitizing effects by impairing Ras family GTPase signaling.
RAS↓,
HMG-CoA↓, Statins are potent, competitive inhibitors of hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase (HMGCR).
HMGCR↓,
LDL↓, Statins reduce blood plasma cholesterol levels by decreasing de novo cholesterol biosynthesis and by inducing changes in low density lipoprotein (LDL) receptor expression [2].
toxicity↓, Due to the well-established safety profile of statins, such studies are less expensive than the development of novel drugs.
Risk↓, statin use in cancer patients was associated with reduced cancer-related mortality. The risk of cancer death was significantly lower in postmenopausal women
P21↑, Other proposed mechanisms leading to an increase of p21 levels include the release of promoter-associated histone deacetylase and inhibition of histone deacetylase
HDAC↓,
Bcl-2↓, Statins trigger the intrinsic apoptosis pathway and decrease Bcl-2 protein expression [[154], [155], [156]], increase Bax and BIM protein expression [[156], [157], [158], [159]], and activate several caspases
BAX↑,
BIM↑,
Casp↑,
cl‑PARP↑, thereby increasing cleaved PARP-1 levels.
MMP↓, different tumor cell lines (breast, brain, and lung) showed that simvastatin-induced apoptosis is dependent on decreasing mitochondrial membrane potential and increasing reactive oxygen species (ROS) production
ROS↑,
angioG↓, Statins inhibit angiogenesis and metastasis
TumMeta↓,
PTEN↑, n breast cancer xenografts, simvastatin prevented tumor growth by reducing Akt phosphorylation and BclXL transcription, while simultaneously increasing the transcription of pro-apoptotic/anti-proliferative PTEN
eff↑, In mice, the administration of a combination of celecoxib and atorvastatin was more effective than each individual treatment, and effectively prevented prostate cancer progression from androgen dependent to androgen independent
OS↑, Long-term statin use may improve survival in GBM patients treated with temozolomide chemotherapy
Remission↑, statin use during or after chemotherapy is not associated with improved disease-free-, recurrence-free-, or overall survival in stage II colon cancer patients

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↓,

2698-

BBR,

A gene expression signature-based approach reveals the mechanisms of action of the Chinese herbal medicine berberine

Analysis,

BC,

MDA-MB-231

HDAC↓, Results showed that BBR may inhibit protein synthesis, histone deacetylase (HDAC), or AKT/mammalian target of rapamycin (mTOR) pathways.
Akt↓,
mTOR↓,
ER Stress↑, BBR inhibited global protein synthesis and basal AKT activity, and induced endoplasmic reticulum (ER) stress and autophagy, which was associated with activation of AMP-activated protein kinase (AMPK).
TumAuto↑,
AMPK↑,
mTOR∅, However, BBR did not alter mTOR or HDAC activities.
HDAC∅, SAHA but not BBR inhibited HDAC activity, suggesting that BBR is not an HDAC inhibitor.
ac‑α-tubulin↑, BBR induced the acetylation of α-tubulin, a substrate of HDAC6, although it did not directly inhibit HDAC activity

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↓,

2697-

BBR,

Structural exploration of common pharmacophore based berberine derivatives as novel histone deacetylase inhibitor targeting HDACs enzymes

Analysis,

Var,

HDAC↓, We derived four berberine derivatives based on common HDAC inhibition pharmacophore

2764-

BetA,

In silico profiling of histone deacetylase inhibitory activity of compounds isolated from Cajanus cajan

Analysis,

Var,

HDAC↓, betulinic acid might be a suitable HDAC inhibitor worthy of further investigation in order to be used for regulating conditions associated with overexpression of HDACs.

3523-

Bor,

Design, Synthesis, and Biological Activity of Boronic Acid-Based Histone Deacetylase Inhibitors

in-vitro,

Var,

HDAC↓, In cancer cell growth inhibition assays, compounds (S)-18, 20, and 21 exerted strong activity, and the values of the ratio of the concentration causing 50% growth inhibition (GI50) to the concentration causing 50% enzyme inhibition

3522-

Bor,

The Boron Advantage: The Evolution and Diversification of Boron’s Applications in Medicinal Chemistry

Review,

Var,

Hif1a↓, One compound, GN26361 (Table 2), potently inhibited the accumulation of HIF-1α under hypoxic conditions via the inhibition of hypoxia-induced HIF-1α transcriptional activity in HeLa cells (IC50 = 0.74 μM) [54].
HDAC↓, Peptidic boronic acids have also been studied for other microbial targets including as a hepatitis C virus (HCV) NS3/4A protease inhibitor [55], an antitubercular drug [56], penicillin-binding proteins [57], histone deacetylase (HDAC) inhibitors [58]
*CXCR2↑, reported boronic acid chemokine antagonist for CXCR 1 and 2 and was able to significantly inhibit inflammation in vivo
ROS↑, In addition to being used as ROS-activated prodrugs, boron-containing drugs have also been modified to form a prodrug, with the intention of increasing the favourability of their pharmacokinetic properties.

696-

Bor,

Nothing Boring About Boron

Review,

Var,

>3mg

upper intake level (UL) of 20 mg/d

*hs-CRP↓, reduces levels of inflammatory biomarkers, such as high-sensitivity C-reactive protein (hs-CRP) and tumor necrosis factor μ (TNF-μ);
*TNF-α↓,
*SOD↑, raises levels of antioxidant enzymes, such as superoxide dismutase (SOD), catalase, and glutathione peroxidase
*Catalase↑,
*GPx↑,
*cognitive↑, improves the brains electrical activity, cognitive performance, and short-term memory for elders; restricted boron intake adversely affected brain function and cognitive performance.
*memory↑, In humans, boron deprivation (<0.3 mg/d) resulted in poorer performance on tasks of motor speed and dexterity, attention, and short-term memory.
*Risk↓, Boron-rich diets and regions where the soil and water are rich in boron correlate with lower risks of several types of cancer, including prostate, breast, cervical, and lung cancers.
*SAM-e↑,
*NAD↝, Boron strongly binds oxidized NAD+,76 and, thus, might influence reactions in which NAD+ is involved
*ATP↝,
*Ca+2↝, Because of its positive charge, magnesium stabilizes cell membranes, balances the actions of calcium, and functions as a signal transducer
HDAC↓, some boronated compounds are histone deacetylase inhibitors
TumVol↓,
IGF-1↓, expression of IGF-1 in the tumors was significantly reduced by boron treatment
PSA↓, Boronic acid has been shown to inhibit PSA activity.
Cyc↓, boric acid inhibits the growth of prostate-cancer cells both by decreasing expression of A-E cyclin
TumCMig↓,
*serineP↓, Boron exists in the human body mostly in the form of boric acid, a serine protease inhibitor.
HIF-1↓, shown to greatly inhibit hypoxia-inducible factor (HIF) 1
*ChemoSideEff↓, An in vitro study found that boric acid can help protect against genotoxicity and cytotoxicity that are induced in lymphocytes by paclitaxel
*VitD↑, greater production of 25-hydroxylase, and, thus, greater potential for vitamin-D activation
*Mag↑, Boron significantly improves magnesium absorption and deposition in bone
*eff↑, boron increases the biological half-life and bioavailability of E2 and vitamin D.
Risk↓, risk of prostate cancer was 52% lower in men whose diets supplied more than 1.8 mg/d of boron compared with those whose dietary boron intake was less than or equal to 0.9 mg/d.
*Inflam↓, As research into the chemistry of boron-containing compounds has increased, they have been shown to be potent antiosteoporotic, anti-inflammatory, and antineoplastic agents
*neuroP↑, In addition, boron has anti-inflammatory effects that can help alleviate arthritis and improve brain function and has demonstrated such significant anticancer
*Calcium↑, increase serum levels of estradiol and calcium absorption in peri- and postmenopausal women.
*BMD↑, boron stimulates bone growth in vitamin-D deficient animals and alleviates dysfunctions in mineral metabolism characteristic of vitamin-D deficiency
*chemoP↑, may help ameliorate the adverse effects of traditional chemotherapeutic agents. boric acid can help protect against genotoxicity and cytotoxicity that are induced in lymphocytes by paclitaxel, an anticancer drug commonly used to treat breast, ovarian
AntiCan↑, demonstrated preventive and therapeutic effects in a number of cancers, such as prostate, cervical, and lung cancers, and multiple and non-Hodgkin’s lymphoma
*Dose↑, only an upper intake level (UL) of 20 mg/d for individuals aged ≥ 18 y.
*Dose↝, substantial number of articles showing benefits support the consideration of boron supplementation of 3 mg/d for any individual who is consuming a diet lacking in fruits and vegetables
*BMPs↑, Boron was also found to increase mRNA expression of alkaline phosphatase and bone morphogenetic proteins (BMPs)
*testos↑, 1 week of boron supplementation of 6 mg/d, a further study by Naghii et al20 of healthy males (n = 8) found (1) a significant increase in free testosterone,
angioG↓, Inhibition of tumor-induced angiogenesis prevents growth of many types of solid tumors and provides a novel approach for cancer treatment; thus, HIF-1 is a target of antineoplastic therapy.
Apoptosis↑, Cancer cells, however, commonly overexpress sugar transporters and/or underexpress borate export, rendering sugar-borate esters as promising chemopreventive agents
*selectivity↑, In normal cells, the 2 latter, cell-destructive effects do not occur because the amount of borate present in a healthy diet, 1 to 10 mg/d, is easily exported from normal cells.
*chemoPv↑, promising chemopreventive agents

5745-

Buty,

Microbial Oncotarget: Bacterial-Produced Butyrate, Chemoprevention and Warburg Effect

Review,

Var,

selectivity↑, Intriguingly, although butyrate promotes proliferation of normal colonocytes, it has the opposite effect on cancerous cells where it inhibits cell proliferation and also induces apoptosis [5]
HDAC↓, functioned as a histone deacetylase (HDAC) inhibitor to regulate genes that inhibited cell proliferation and promoted apoptosis
TumCP↓,
Apoptosis↑,
Warburg↓, ability to prevent the Warburg effect from occurring in cancerous colonocytes by performing RNAi to deplete an important mediator of the Warburg effect (LDHA)
chemoPv↑, Chemoprevention

5743-

Buty,

Regulation of Intestinal Butyrate Transporters by Oxidative and Inflammatory Status

Review,

Var,

*GutMicro↑, Beneficial effects of the microbiota-derived metabolite butyrate at the colonic level are well established, particularly through its relevance in colorectal cancer (CRC) and inflammatory bowel disease (IBD)
*other↑, (2) stimulates growth and proliferation of normal intestinal epithelial cells;
*Inflam↓, (3) inhibits inflammation;
*ROS↓, (4) inhibits oxidative stress;
AntiCan↑, (8) inhibits colon carcinogenesis
HCAR2↑, three cell-surface G-protein-coupled receptors, GPR41, GPR43, and GPR109A, are targets for butyrate [1,2].
HDAC↓, butyrate also has intracellular actions (HDAC inhibition),

5742-

Buty,

Butyrate: A Double-Edged Sword for Health?

Review,

Var,

HCAR2↑, Another major GPCR activated by butyrate is GPR109A (
Inflam↓, anti-inflammatory properties of butyrate are also achieved through inhibition of the production of proinflammatory enzymes and cytokines
HDAC↓, Butyrate functions as an HDAC inhibitor
*IFN-γ↓, animal studies reported that the proinflammatory cytokines IFN-γ, TNF-α, IL-1β, IL-6, and IL-8 are inhibited, whereas IL-10 and TGF-β are upregulated in response to butyrate
*TNF-α↓,
*IL1β↓,
*IL6↓,
*IL8↓,
*IL10↑,
*TNF-β↑,
*NF-kB↓, butyrate is at least in part due to inhibition of the activation of a transcription factor known as NF-κB (
*ROS↓, by rescuing the redox machinery and controlling reactive oxygen species,
PPARγ↓, Further studies also showed that butyrate is capable of activating PPAR-γ (67), which is a member of the nuclear hormone receptor family and highly expressed in colonic epithelial cells,
Weight↓, although a large body of evidence has suggested the effect of butyrate on alleviating high fat diet–induced obesity and insulin resistance, a few studies showed an opposite effect.

5740-

Buty,

A Review of Nutritional Regulation of Intestinal Butyrate Synthesis: Interactions Between Dietary Polysaccharides and Proteins

Review,

RCC,

*eff↓, excessive protein fermentation produces branched-chain fatty acid (BCFA), ammonia, phenols, and other metabolites that inhibit butyrate production
Dose↝, Several studies have found that the ratio of acetate to propionate to butyrate in the colon of healthy individuals (regardless of region) has been found to be approximately 60:20:20 [2,3].
eff↑, An appropriate polysaccharide-to-protein ratio appears crucial for maintaining gut microbial homeostasis and facilitating butyrate generation.
HDAC↓, butyrate is a classic HDAC inhibitor that increases the acetylation level of histone H3 and H4,
ac‑H3↓,
ac‑H4↓,
*HCAR2↑, butyrate is produced by the gut microbiota at high concentrations (10–20 mM) and acts as an endogenous agonist of GPR109A.
*Inflam↓, When butyrate activates GPR109A on colonocytes, it triggers intracellular signaling cascades, promotes the secretion of the anti-inflammatory cytokine IL-18,
*ROS↓, Moreover, butyrate reduces the level of reactive oxygen species by activating the Nrf2 antioxidant pathway and enhancing glutathione (GSH) synthesis, and alleviate stress damage to the to intestinal barrier and immune cells.
*NRF2↑,
*GSH↑,
*CLDN1↑, Butyrate also enhances epithelial barrier function by upregulating the expression of tight junction proteins such as Claudin-1, Occludin, and ZO-1 in intestinal epithelial cells.
*ZO-1↑,
IL1β↓, rucial role in repairing and strengthening the intestinal barrier by downregulating the transcription of pro-inflammatory genes, including IL-1β, IL-6, and COX-2,
IL6↓,
COX2↓,
eff↝, Different types of monosaccharides significantly influence the efficiency of butyrate production due to their distinct chemical properties and microbial utilization mechanisms.
eff↑, After entering the colon, polysaccharides serve as fermentation substrates for gut microbiota and are broken down into butyrate.
other↝, A central challenge in current research on gut microbiota and butyrate production lies in determining the optimal dietary ratio of polysaccharides to proteins.

5739-

Buty,

Butyrate as a promising therapeutic target in cancer: From pathogenesis to clinic (Review)

Review,

Var,

GutMicro↑, Butyrate, a short-chain fatty acid, is generated through gut microbial fermentation of dietary fiber.
*Inflam↓, Butyrate, a primary anti-inflammatory SCFA, exhibits a multifaceted role in mitigating inflammation
*IL6↓, It inhibits the production of pro-inflammatory cytokines and chemokines, such as IL-6, TNF-α and IL-17, which helps to prevent colon cancer
*TNF-α↓,
*IL17↓,
*IL10↑, while promoting IL-10 production
*ROS↝, regulates the production of reactive oxygen species (ROS)
COX2↓, butyrate has been observed to suppress inflammation by inhibiting the expression of cyclooxygenase-2 mRNA in colonic tissues (60).
NLRP3↓, butyrate exhibits the highest efficiency in the negative regulation of NLRP3
Imm↑, Enhancement of the immunotherapeutic effect
HDAC↓, Inhibition of HDAC activity in cells
TumCCA↑, Butyrate has been found to induce cell cycle arrest in the G0/G1 phase in a dose-dependent manner in vitro in numerous tumors, including colon, liver, lung and bladder cancer,
Apoptosis↑, butyrate-induced apoptosis is accompanied by elevated ROS levels and caspase activity (126)
ROS↑,
Casp↑,
mtDam↑, suggests that ROS can induce mitochondrial membrane damage, release Cyt c from damaged mitochondria, and enhance apoptosis via the Cyt c/caspase-3 pathway
Cyt‑c↑,
eff↑, Clostridium butyricum is an anaerobic bacterium classified as a probiotic due to its production of butyric acid (139)
chemoP↑, butyrate not only alleviates the side effects associated with conventional chemotherapeutic agents such as oxaliplatin, irinotecan and 5-fluorouracil (149-151), but it also enhances the efficacy of both chemotherapy and immunotherapy
ChemoSen↑,
eff↑, metformin has been demonstrated to enhance the biosynthesis of butyrate while concurrently inhibiting the progression of CRC
RadioS↑, Butyrate significantly enhanced radiation-induced cell death and enhanced treatment effects compared with administration of radiation alone.
HCAR2↑, Activation of cell-surface receptors (GPR41, GPR43 and GPR109A);

5732-

Buty,

GPR109A is a G-protein-coupled receptor for the bacterial fermentation product butyrate and functions as a tumor suppressor in colon

Study,

CRC,

Human colonic biopsies were obtained during colonoscopy

HCAR2↑, Millimolar concentrations of butyrate are needed to activate the receptor.
other↓, The expression of GPR109A is silenced in colon cancer in humans, in a mouse model of intestinal/colon cancer, and in colon cancer cell lines.
Apoptosis↑, Re-expression of GPR109A in colon cancer cells induces apoptosis, but only in the presence of its ligands butyrate and nicotinate.
HDAC↓, Butyrate is an inhibitor of histone deacetylases, but apoptosis induced by activation of GPR109A with its ligands in colon cancer cells does not involve inhibition of histone deacetylation.
Bcl-2↓, primary changes in this apoptotic process include downregulation of Bcl-2, Bcl-xL, and cyclin D1, and upregulation of death receptor pathway.
Bcl-xL↓,
cycD1/CCND1↓,
DR5↑,
NF-kB↓, In addition, GPR109A/butyrate suppresses NF-κB activation in normal and cancer colon cell lines as well as in normal mouse colon.
GutMicro↑, Gut bacteria play a critical role in the prevention of colon cancer and inflammatory bowel disease
SLC12A5↝, We have shown previously that butyrate induces apoptosis in colon cancer cell lines if SLC5A8, a butyrate transporter, is expressed in these cells and that the process is associated with inhibition of HDACs

5731-

Buty,

The Warburg Effect Dictates the Mechanism of Butyrate Mediated Histone Acetylation and Cell Proliferation

in-vitro,

CRC,

HCT116

in-vitro,

CRC,

HT29

HDAC↓, butyrate accumulated and functioned as an HDAC inhibitor.
Warburg↓, Consequently, butyrate stimulated the proliferation of normal colonocytes and cancerous colonocytes when the Warburg effect was prevented from occurring, whereas it inhibited the proliferation of cancerous colonocytes undergoing the Warburg effect.
TumCP⇅, Butyrate Increases or Decreases Cell Proliferation Depending on the Warburg Effect
HATs↑, Butyrate Induces Histone Acetylation by Stimulating HATs as well as Inhibiting HDACs
BioAv↓, However, the efficacy of butyrate as a chemotherapeutic agent has been limited by its rapid uptake and metabolism by normal cells [resulting in a half-life of 6 minutes and peak blood levels below 0.05 mM (Miller et al., 1987)] before reaching tumors
other↝, A fiber-rich diet might be more successful for chemoprevention because it delivers mM levels of butyrate (via the microbiota) to the correct place (the colon) before the onset of tumorigenesis or at an early stage.
Risk↓, Evidence for this idea comes from recent human studies demonstrating lower levels of butyrate-producing bacteria among the gut microbiota of colorectal cancer patients compared to healthy participants

5737-

Buty,

Butyrate Suppresses the Proliferation of Colorectal Cancer Cells via Targeting Pyruvate Kinase M2 and Metabolic Reprogramming

in-vitro,

CRC,

HCT116

HDAC↓, thereby functioning as an HDAC inhibitor to inhibit the proliferation of colorectal cancer cells.
TumCP↓, butyrate significantly inhibited the proliferation of HCT116 cells in a dose-dependent manner
PKM2↑, suggested that butyrate binds to and activates pyruvate kinase isoform 2 (PKM2), which is subsequently responsible for reversing the metabolic advantages gained by cancerous colonocytes and ultimately leads to proliferation arrest.
Warburg↓, Butyrate Suppresses the Warburg Effect in Colorectal Cancer Cells

2050-

Buty,

The Role of Sodium Phenylbutyrate in Modifying the Methylome of Breast Cancer Cells

in-vitro,

BC,

MCF-7

3μM and 5μM

eff↑, most effective treatment was sodium phenylbutyrate when used alone in a low dose (3μM)
HDAC↓, Sodium phenylbutyrate, (representative to HDAC Inhibitor)
TumCG↓, sodium phenylbutyrate solely at its low concentrations, i.e., 3μM a potential treatment to withhold breast cancer cells

2047-

Buty,

Sodium butyrate inhibits migration and induces AMPK-mTOR pathway-dependent autophagy and ROS-mediated apoptosis via the miR-139-5p/Bmi-1 axis in human bladder cancer cells

in-vitro,

CRC,

T24/HTB-9

0-10mM

in-vitro,

Nor,

SV-HUC-1

in-vitro,

Bladder,

5637

in-vivo,

NA,

200 mg/kg/day, i.g., n = 5

mice

HDAC↓, Sodium butyrate (NaB) is a histone deacetylase inhibitor and exerts remarkable antitumor effects in various cancer cells
AntiTum↑,
TumCMig↓, NaB inhibited migration
AMPK↑, induced AMPK/mTOR pathway-activated autophagy and reactive oxygen species (ROS) overproduction via the miR-139-5p/Bmi-1 axis
mTOR↑,
TumAuto↑,
ROS↑, NaB initiates ROS overproduction
miR-139-5p↑, NaB upregulates miR-139-5p and depletes Bmi-1 in bladder cancer cells
BMI1↓,
TumCI?, NaB significantly inhibited cell migration dose-dependently
E-cadherin↑, E-cadherin was markedly increased, while the expression of N-cadherin, Vimentin, and Snail was decreased
N-cadherin↓,
Vim↓,
Snail↓,
cl‑PARP↑, increased expression levels of cleaved PARP, cleaved caspase-3, and Bax and the concurrent decrease in Bcl-2 and Bcl-xl
cl‑Casp3↑,
BAX↑,
Bcl-2↓,
Bcl-xL↓,
MMP↓, impairs mitochondrial membrane potential
PINK1↑, activates the PINK1/ PARKIN pathway
PARK2↑,
TumMeta↓, NaB inhibits tumor metastasis and growth in vivo
TumCG↓,
LC3II↑, a significant increase in the levels of cleaved caspase3, p-AMPK, and LC3B-II along with decreased Bmi-1 and Vimentin
p62↓, elevated LC3B-II levels and degradation of p62
eff↓, NAC abolished the impairment of MMP and ROS overproduction. Interestingly, NAC also significantly inhibited apoptosis induced by NaB

1080-

Buty,

Butyrate suppresses Cox-2 activation in colon cancer cells through HDAC inhibition

in-vitro,

CRC,

HT-29

HDAC↓, HDAC inhibitors butyrate
TNF-α↓,
COX2↓,

2798-

CHr,

Chrysin: a histone deacetylase 8 inhibitor with anticancer activity and a suitable candidate for the standardization of Chinese propolis

in-vitro,

BC,

MDA-MB-231

in-vivo,

NA,

90 mg/kg/day

xenograft animal model

HDAC↓, chrysin is a histone deacetylase inhibitor (HDACi) and that it markedly inhibited HDAC8 enzymatic activity
HDAC8↓,
TumCG↓, chrysin significantly suppressed cell growth and induced differentiation in MDA-MB-231 cells
Diff↑,

2784-

CHr,

Chrysin targets aberrant molecular signatures and pathways in carcinogenesis (Review)

Review,

Var,

Apoptosis↑, apoptosis, disrupting the cell cycle and inhibiting migration without generating toxicity or undesired side‑effects in normal cells
TumCMig↓,
*toxicity↝, toxic at higher doses and the recommended dose for chrysin is <3 g/day
ChemoSen↑, chrysin also inhibits multi‑drug resistant proteins and is effective in combination therapy
*BioAv↓, extremely low bioavailability in humans due to rapid quick metabolism, removal and restricted assimilation. The bioavailability of chrysin when taken orally has been estimated to be between 0.003 to 0.02%
Dose↝, safe and effective in various studies where volunteers have taken oral doses ranging from 300 to 625 mg without experiencing any documented effect
neuroP↑, Chrysin has been shown to exert neuroprotective effects via a variety of mechanisms, such as gamma-aminobutyric acid mimetic properties, monoamine oxidase inhibition, antioxidant, anti-inflammatory and anti-apoptotic activities
*P450↓, Chrysin inhibits cytochrome P450 2E1, alcohol dehydrogenase and xanthine oxidase at various dosages (20 and 40 mg/kg body weight) and protects Wistar rats against oxidative stress
*ROS↓,
*HDL↑, ncreased the levels of high-density lipoprotein cholesterol, glutathione S-transferase, superoxide dismutase and catalase
*GSTs↑,
*SOD↑,
*Catalase↑,
*MAPK↓, inactivate the MAPK/JNK pathway and suppress the NF-κB pathways, and at the same time upregulate the expression of PTEN, and activate the VEGF/AKT pathway
*NF-kB↓,
*PTEN↑,
*VEGF↑,
ROS↑, chrysin treatment in ovarian cancer led to the augmented generation of reactive oxygen species, a decrease in MMP and an increase in cytoplasmic Ca2+,
MMP↓,
Ca+2↑,
selectivity↑, It has been found that chrysin has no cytotoxic effect on normal cells, such as fibroblasts
PCNA↓, Chrysin likewise downregulates proliferating cell nuclear antigen (PCNA) expression in cervical carcinoma cells
Twist↓, Chrysin decreases the expression of TWIST 1 and NF-κB and thus suppresses epithelial-mesenchymal transition (EMT) in HeLa cells
EMT↓,
CDKN1C↑, Chrysin administration led to the upregulation of CDKN1 at the transcript and protein leve
p‑STAT3↑, Chrysin decreased the viability of 4T1 breast cancer cells by suppressing hypoxia-induced phosphorylation of STAT3
MMP2↓, chrysin-loaded PGLA/PEG nanoparticles modulated TIMPS and MMP2 and 9, and PI3K expression in a mouse 4T1 breast tumor model
MMP9↓,
eff↑, Chrysin used alone and as an adjuvant with metformin has been found to downregulate cyclin D and hTERT expression in the breast cancer cell line
cycD1/CCND1↓,
hTERT/TERT↓,
CLDN1↓, CLDN1 and CLDN11 expression have been found to be higher in human lung squamous cell carcinoma. Treatment with chrysin treatment reduces both the mRNA and protein expression of these claudin genes
TumVol↓, Treatment with chrysin treatment (1.3 mg/kg body weight) significantly decreases tumor volume, resulting in a 52.6% increase in mouse survival
OS↑,
COX2↓, Chrysin restores the cellular equilibrium of cells subjected to benzopyrene by downregulating the expression of elevated proteins, such as PCNA, NF-κB and COX-2
eff↑, quercetin and chrysin together decreased the levels of pro-inflammatory molecules, such as IL-6, -1 and -10, and the levels of TNF via the NF-κB pathway.
CDK2↓, Chrysin has been shown to inhibit squamous cell carcinoma via the modulation of Rb and by decreasing the expression of CDK2 and CDK4
CDK4↓,
selectivity↑, chrysin selectively exhibits toxicity and induces the self-programed death of human uveal melanoma cells (M17 and SP6.5) without having any effect on normal cells
TumCCA↑, halting the cell cycle at the G2/M or G1/S phases
E-cadherin↑, upregulation of E-cadherin and the downregulation of cadherin
HK2↓, Chrysin decreased expression of HK-2 in mitochondria, and the interaction between HK-2 and VDAC 2 was disrupted,
HDAC↓, Chrysin, a HDAC inhibitor, caused cytotoxicity, and also inhibited migration and invasion.

2785-

CHr,

Emerging cellular and molecular mechanisms underlying anticancer indications of chrysin

Review,

Var,

*NF-kB↓, suppressed pro-inflammatory cytokine expression and histamine release, downregulated nuclear factor kappa B (NF-kB), cyclooxygenase 2 (COX-2), and inducible nitric oxide synthase (iNOS)
*COX2↓,
*iNOS↓,
angioG↓, upregulated apoptotic pathways [28], inhibited angiogenesis [29] and metastasis formation
TOP1↓, suppressed DNA topoisomerases [31] and histone deacetylase [32], downregulated tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β)
HDAC↓,
TNF-α↓,
IL1β↓,
cardioP↑, promoted protective signaling pathways in the heart [34], kidney [35] and brain [8], decreased cholesterol level
RenoP↑,
neuroP↑,
LDL↓,
BioAv↑, bioavailability of chrysin in the oral route of administration was appraised to be 0.003–0.02% [55], the maximum plasma concentration—12–64 nM
eff↑, Chrysin alone and potentially in combination with metformin decreased cyclin D1 and hTERT gene expression in the T47D breast cancer cell line
cycD1/CCND1↓,
hTERT/TERT↓,
MMP-10↓, Chrysin pretreatment inhibited MMP-10 and Akt signaling pathways
Akt↓,
STAT3↓, Chrysin declined hypoxic survival, inhibited activation of STAT3, and reduced VEGF expression in hypoxic cancer cells
VEGF↓,
EGFR↓, chrysin to inhibit EGFR was reported in a breast cancer stem cell model [
Snail↓, chrysin downregulated MMP-10, reduced snail, slug, and vimentin expressions increased E-cadherin expression, and inhibited Akt signaling pathway in TNBC cells, proposing that chrysin possessed a reversal activity on EMT
Slug↓,
Vim↓,
E-cadherin↑,
eff↑, Fabrication of chrysin-attached to silver and gold nanoparticles crossbred reduced graphene oxide nanocomposites led to augmentation of the generation of ROS-induced apoptosis in breast cancer
TET1↑, Chrysin induced augmentation in TET1
ROS↑, Pretreatment with chrysin induced ROS formation, and consecutively, inhibited Akt phosphorylation and mTOR.
mTOR↓,
PPARα↓, Chrysin inhibited mRNA expression of PPARα
ER Stress↑, ROS production by chrysin was the critical mediator behind induction of ER stress, leading to JNK phosphorylation, intracellular Ca2+ release, and activation of the mitochondrial apoptosis pathway
Ca+2↑,
ERK↓, reduced protein expression of p-ERK/ERK
MMP↑, Chrysin pretreatment led to an increase in mitochondrial ROS creation, swelling in isolated mitochondria from hepatocytes, collapse in MMP, and release cytochrome c.
Cyt‑c↑,
Casp3↑, Chrysin could elevate caspase-3 activity in the HCC rats group
HK2↓, chrysin declined HK-2 combined with VDAC-1 on mitochondria
NRF2↓, chrysin inhibited the Nrf2 expression and its downstream genes comprising AKR1B10, HO-1, and MRP5 by quenching ERK and PI3K-Akt pathway
HO-1↓,
MMP2↓, Chrysin pretreatment also downregulated MMP2, MMP9, fibronectin, and snail expression
MMP9↓,
Fibronectin↓,
GRP78/BiP↑, chrysin induced GRP78 overexpression, spliced XBP-1, and eIF2-α phosphorylation
XBP-1↓,
p‑eIF2α↑,
*AST↓, Chrysin administration significantly reduced AST, ALT, ALP, LDH and γGT serum activities
ALAT↓,
ALP↓,
LDH↓,
COX2↑, chrysin attenuated COX-2 and NFkB p65 expression, and Bcl-xL and β-arrestin levels
Bcl-xL↓,
IL6↓, Reduction in IL-6 and TNF-α and augmentation in caspases-9 and 3 were observed due to chrysin supplementation.
PGE2↓, Chrysin induced entire suppression NF-kB, COX-2, PG-E2, iNOS as well.
iNOS↓,
DNAdam↑, Chrysin induced apoptosis of cells by causing DNA fragmentation and increasing the proportions of DU145 and PC-3 cells
UPR↑, Also, it induced ER stress via activation of UPR proteins comprising PERK, eIF2α, and GRP78 in DU145 and PC-3 cells.
Hif1a↓, Chrysin increased the ubiquitination and degradation of HIF-1α by increasing its prolyl hydroxylation
EMT↓, chrysin was effective in HeLa cell by inhibiting EMT and CSLC properties, NF-κBp65, and Twist1 expression
Twist↓,
lipid-P↑, Chrysin disrupted intracellular homeostasis by altering MMP, cytosolic Ca (2+) levels, ROS generation, and lipid peroxidation, which plays a role in the death of choriocarcinoma cells.
CLDN1↓, Chrysin decreased CLDN1 and CLDN11 expression in human lung SCC
PDK1↓, Chrysin alleviated p-Akt and inhibited PDK1 and Akt
IL10↓, Chrysin inhibited cytokines release, TNF-α, IL-1β, IL-10, and IL-6 induced by Ni in A549 cells.
TLR4↓, Chrysin suppressed TLR4 and Myd88 mRNA and protein expression.
NOTCH1↑, Chrysin inhibited tumor growth in ATC both in vitro and in vivo through inducing Notch1
PARP↑, Pretreating cells with chrysin increased cleaved PARP, cleaved caspase-3, and declined cyclin D1, Mcl-1, and XIAP.
Mcl-1↓,
XIAP↓,

2794-

CHr,

An updated review on the versatile role of chrysin in neurological diseases: Chemistry, pharmacology, and drug delivery approaches

Review,

Park,

Review,

Stroke,

*neuroP↑, chrysin has protective effects against neurological conditions by modulating oxidative stress, inflammation, and apoptosis in animal models.
*ROS↓,
*Inflam↓,
*Apoptosis↓,
*IL1β↓, attenuated IL-1β and TNF-α, COX-2, iNOS, and NF-kB expression, activated JNK
*TNF-α↓,
*COX2↓,
*iNOS↓,
*NF-kB↓,
*JNK↓,
*HDAC↓, alleviated histone deacetylase (HDCA) activity, GSK-3β levels, IFNγ, IL-17,
*GSK‐3β↓,
*IFN-γ↓,
*IL17↓,
*GSH↑, increased GSH levels
*NRF2↑, Park's: Increased Nrf2, modulated HO-1, SOD, CAT, decreased MDA, inhibited NF-κB and iNOS
*HO-1↑, upregulated expression of hallmark antioxidant enzymes, including HO-1, SOD, and CAT; and decreased levels of MDA
*SOD↑,
*MDA↓,
*NO↓, Attenuated NO, increased GPx
*GPx↑,
*TBARS↓, decreased levels of TBARS, AChE, restored activities of GR, GSH, SOD, CAT and Vitamin C
*AChE↓,
*GR↑,
*Catalase↑,
*VitC↑,
*memory↑, attenuated memory impairment
*lipid-P↓, attenuated lipid peroxidation
*ROS↓, attenuated ROS

1505-

CUR,

Epigenetic targets of bioactive dietary components for cancer prevention and therapy

Review,

NA,

25 μM @24hr

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

163-

CUR,

Epigenetic CpG Demethylation of the Promoter and Reactivation of the Expression of Neurog1 by Curcumin in Prostate LNCaP Cells

in-vitro,

Pca,

LNCaP

 5 μM CUR for 7 days

MeCP2↓, decreased the MeCP2-Neurog1 binding dramatically
Neurog1↑, our present study provides evidence on the CpG demethylation ability of CUR on Neurog1 while activating its expression
HDAC↓, CUR Treatment Decreases the Total HDAC Activity (50%)

4826-

CUR,

The Bright Side of Curcumin: A Narrative Review of Its Therapeutic Potential in Cancer Management

Review,

Var,

*antiOx↑, Curcumin demonstrates strong antioxidant and anti-inflammatory properties, contributing to its ability to neutralize free radicals and inhibit inflammatory mediators
*Inflam↑,
*ROS↓,
Apoptosis↑, Its anticancer effects are mediated by inducing apoptosis, inhibiting cell proliferation, and interfering with tumor growth pathways in various colon, pancreatic, and breast cancers
TumCP↓,
BioAv↓, application is limited by its poor bioavailability due to its rapid metabolism and low absorption.
Half-Life↓,
eff↑, curcumin-loaded hydrogels and nanoparticles, have shown promise in improving curcumin bioavailability and therapeutic efficacy.
TumCCA↑, Studies have demonstrated that curcumin can suppress the proliferation of cancer cells by interfering with the cell cycle [21,22]
BAX↑, Curcumin enhances the expression of pro-apoptotic proteins such as Bax, Bak, PUMA, Bim, and Noxa and death receptors such as TRAIL-R1/DR4 and TRAIL-R2/DR5
Bak↑,
PUMA↑,
BIM↑,
NOXA↑,
TRAIL↑,
Bcl-2↓, curcumin decreases the levels of anti-apoptotic proteins like Bcl-2, Bcl-XL, survin, and XIAP
Bcl-xL↓,
survivin↓,
XIAP↓,
cMyc↓, This shift in the balance of apoptotic regulators facilitates the release of cytochrome c from mitochondria [33,35] and activates caspases
Casp↑,
NF-kB↓, Curcumin suppresses the activity of key transcription factors like NF-κB, STAT3, and AP-1 and interferes with critical signal transduction pathways such as PI3K/Akt/mTOR and MAPK/ERK.
STAT3↓,
AP-1↓,
angioG↓, curcumin inhibits angiogenesis and metastasis by downregulating VEGF, VEGFR2, and matrix metalloproteinases (MMPs).
TumMeta↑,
VEGF↓,
MMPs↓,
DNMTs↓, Epigenetic modifications through the inhibition of DNA methyltransferases (DNMTs) and histone deacetylases (HDACs) further contribute to its anticancer properties.
HDAC↓,
ROS↑, curcumin-loaded nanoparticles showed significant cytotoxicity in the SCC25, MDA-MB-231, and A549 cell lines, with a decrease in tumor cell proliferation, an increase in ROS, and an increase in apoptosis.

1863-

dietFMD,

Chemo,

Effect of fasting on cancer: A narrative review of scientific evidence

Review,

Var,

eff↑, recommend combining prolonged periodic fasting with a standard conventional therapeutic approach to promote cancer‐free survival, treatment efficacy, and reduce side effects in cancer patients.
ChemoSideEff↓, lowered levels of IGF1 and insulin have the potential to protect healthy cells from side effects
ChemoSen↑,
Insulin↓, causes insulin levels to drop and glucagon levels to rise
HDAC↓, Histone deacetylases are inhibited by ketone bodies, which may slow tumor development.
IGF-1↓, FGF21 rises during intermittent fasting, and it plays a vital role in lowering IGF1 levels by inhibiting phosphorylated STAT5 in the liver
STAT5↓,
BG↓, Fasting suppresses glucose, IGF1, insulin, the MAPK pathway, and heme oxygenase 1
MAPK↓,
HO-1↓,
ATG3↑, while increasing many autophagy‐regulating components (Atgs, LC3, Beclin1, p62, Sirt1, and LAMP2).
Beclin-1↑,
p62↑,
SIRT1↑,
LAMP2↑,
OXPHOS↑, Fasting causes cancer cells to release oxidative phosphorylation (OXPHOS) through aerobic glycolysis
ROS↑, which leads to an increase in reactive oxygen species (ROS), p53 activation, DNA damage, and cell death in response to chemotherapy.
P53↑,
DNAdam↑,
TumCD↑,
ATP↑, and causes extracellular ATP accumulation, which inhibits Treg cells and the M2 phenotype while activating CD8+ cytotoxic T cells.
Treg lymp↓,
M2 MC↓,
CD8+↑,
Glycolysis↓, By lowering glucose intake and boosting fatty acid oxidation, fasting can induce a transition from aerobic glycolysis to mitochondrial oxidative phosphorylation in cancerous cells, resulting in increased ROS
GutMicro↑, Fasting has been shown to have a direct impact on the gut microbial community's constitution, function, and interaction with the host, which is the complex and diverse microbial population that lives in the intestine
GutMicro↑, Fasting also reduces the number of potentially harmful Proteobacteria while boosting the levels of Akkermansia muciniphila.
Warburg↓, Fasting generates an anti‐Warburg effect in colon cancer models, which increases oxygen demand but decreases ATP production, indicating an increase in mitochondrial uncoupling.
Dose↝, Those patients fasted for 36 h before treatment and 24 h thereafter, having a total of 350 calories per day. Within 8 days of chemotherapy, no substantial weight loss was recorded, although there was an improvement in quality of life and weariness.

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↑,

3230-

EGCG,

Green Tea Polyphenol Epigallocatechin 3-Gallate, Contributes to the Degradation of DNMT3A and HDAC3 in HCT 116 Human Colon Cancer Cells

in-vitro,

CRC,

HCT116

50 μM to 150 μM

in-vitro,

CRC,

HT29

HDAC↓, HDAC and DNMT protein expression was reduced when methylation-sensitive HCT 116 human colon cancer cells was treated with EGCG, but was relatively stable in the HT-29 cell line.
DNMTs↓,

3229-

EGCG,

Epigallocatechin-3-gallate (EGCG) Alters Histone Acetylation and Methylation and Impacts Chromatin Architecture Profile in Human Endothelial Cells

in-vitro,

Nor,

HMEC

in-vitro,

Nor,

HUVECs

HDAC↓, We also found that the catechin acts as an HDAC inhibitor in cellular and cell-free models

3231-

EGCG,

Epigallocatechin-3-gallate restores mitochondrial homeostasis impairment by inhibiting HDAC1-mediated NRF1 histone deacetylation in cardiac hypertrophy

in-vitro,

Nor,

*HDAC↓, Administration of epigallocatechin-3-gallate (EGCG), an inhibitor of HDAC1, restored cardiac function, decreased heart/body weight and fibrosis
*cardioP↑,
*Nrf1↑, EGCG upregulated both NRF1 and PGC-1α in vitro
*PGC-1α↓,

3235-

EGCG,

(-)-Epigallocatechin-3-gallate reverses the expression of various tumor-suppressor genes by inhibiting DNA methyltransferases and histone deacetylases in human cervical cancer cells

in-vivo,

Cerv,

HeLa

DNMTs↓, In the present study, time-dependent EGCG-treated HeLa cells were found to have a significant reduction in the enzymatic activity of DNMT and HDAC
HDAC↓,

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↑,

3237-

EGCG,

(-)-Epigallocatechin-3-gallate attenuates cognitive deterioration in Alzheimer's disease model mice by upregulating neprilysin expression

in-vivo,

AD,

intragastric administration of low- and high-dose EGCG (5 and 15 mg/kg, respectively) for 60 day

*HDAC↓, We previously reported that (-)-epigallocatechin-3-gallate (EGCG) acts as an HDAC inhibitor
*Aβ↓, Here, we demonstrate that EGCG reduced β-amyloid (Aβ) accumulation in vitro and rescued cognitive deterioration in senescence-accelerated mice
cognitive↑,

3238-

EGCG,

Green tea catechin, epigallocatechin-3-gallate (EGCG): mechanisms, perspectives and clinical applications

Review,

Var,

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↑,
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↓, EGCG reduces the activity of COX-2 following interleukin-1A stimulation of human chondrocytes
angioG↓, EGCG inhibits angiogenesis by enhancing FOXO transcriptional activity

Showing Research Papers: 1 to 50 of 144
Page 1 of 3 Next

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 144

Pathway results for Effect on Cancer / Diseased Cells:

Infection & Microbiome ⓘ

CD8+↑, 1,
Total Targets: 266

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

antiOx↑, 3, Catalase↑, 3, GPx↑, 2, GSH↑, 2, GSTs↑, 1, HDL↑, 1, HO-1↑, 1, lipid-P↓, 1, MDA↓, 1, Nrf1↑, 1, NRF2↑, 3, ROS↓, 8, ROS↝, 1, SAM-e↑, 1, SOD↑, 3, TBARS↓, 1, VitC↑, 1,

Mitochondria & Bioenergetics ⓘ

ATP↑, 1, ATP↝, 1, PGC-1α↓, 1,

Core Metabolism/Glycolysis ⓘ

NAD↝, 1,

Cell Death ⓘ

Apoptosis↓, 1, iNOS↓, 2, JNK↓, 1, MAPK↓, 1,

Kinase & Signal Transduction ⓘ

HCAR2↑, 1,

Transcription & Epigenetics ⓘ

other↑, 1,

DNA Damage & Repair ⓘ

DNMT1↓, 1, DNMT3A↓, 1,

Proliferation, Differentiation & Cell State ⓘ

GSK‐3β↓, 1, HDAC↓, 4, PTEN↑, 1,

Migration ⓘ

Ca+2↝, 1, CLDN1↑, 1, serineP↓, 1, ZO-1↑, 1,

Angiogenesis & Vasculature ⓘ

NO↓, 1, VEGF↑, 1,

Immune & Inflammatory Signaling ⓘ

COX2↓, 2, CXCR2↑, 1, HCAR2↑, 1, IFN-γ↓, 2, IL10↑, 2, IL17↓, 2, IL1β↓, 2, IL6↓, 2, IL8↓, 1, Inflam↓, 6, Inflam↑, 1, NF-kB↓, 4, TNF-α↓, 4, TNF-β↑, 1, VitD↑, 1,

Synaptic & Neurotransmission ⓘ

AChE↓, 1,

Protein Aggregation ⓘ

Aβ↓, 1,

Hormonal & Nuclear Receptors ⓘ

GR↑, 1, testos↑, 1,

Drug Metabolism & Resistance ⓘ

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

Clinical Biomarkers ⓘ

AST↓, 1, BMD↑, 1, BMPs↑, 1, Calcium↑, 1, GutMicro↑, 1, hs-CRP↓, 1, IL6↓, 2, Mag↑, 1, VitD↑, 1,

Functional Outcomes ⓘ

AntiCan↑, 1, cardioP↑, 2, chemoP↑, 1, chemoPv↑, 1, ChemoSideEff↓, 1, cognitive↑, 1, memory↑, 2, neuroP↑, 2, Risk↓, 1, toxicity↝, 1,
Total Targets: 83

Scientific Paper Hit Count for: HDAC, Histone deacetylases

32 Sulforaphane (mainly Broccoli)
23 Phenylbutyrate
14 Thymoquinone
12 Butyrate
9 EGCG (Epigallocatechin Gallate)
7 Apigenin (mainly Parsley)
4 Chrysin
4 Chemotherapy
4 Luteolin
4 Quercetin
3 Berberine
3 Boron
3 Curcumin
3 Honokiol
3 Resveratrol
3 Silymarin (Milk Thistle) silibinin
2 Ashwagandha(Withaferin A)
2 Atorvastatin
2 Cisplatin
2 Propolis -bee glue
2 Phenethyl isothiocyanate
1 3-bromopyruvate
1 Allicin (mainly Garlic)
1 Acetyl-l-carnitine
1 alpha Linolenic acid
1 Andrographis
1 Betulinic acid
1 diet FMD Fasting Mimicking Diet
1 Emodin
1 Genistein (soy isoflavone)
1 Magnolol
1 Radiotherapy/Radiation
1 Piperlongumine
1 Vorinostat
1 diet Plant based
1 Gemcitabine (Gemzar)
1 Vitamin D3
1 doxorubicin
1 Selenite (Sodium)

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

HDAC Cancer Research Results

Pathway results for Effect on Cancer / Diseased Cells:

Redox & Oxidative Stress ⓘ

Mitochondria & Bioenergetics ⓘ

Core Metabolism/Glycolysis ⓘ

Cell Death ⓘ

Kinase & Signal Transduction ⓘ

Transcription & Epigenetics ⓘ

Protein Folding & ER Stress ⓘ

Autophagy & Lysosomes ⓘ

DNA Damage & Repair ⓘ

Cell Cycle & Senescence ⓘ

Proliferation, Differentiation & Cell State ⓘ

Migration ⓘ

Angiogenesis & Vasculature ⓘ

Barriers & Transport ⓘ

Immune & Inflammatory Signaling ⓘ

Protein Aggregation ⓘ

Hormonal & Nuclear Receptors ⓘ

Drug Metabolism & Resistance ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

Infection & Microbiome ⓘ

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

Mitochondria & Bioenergetics ⓘ

Core Metabolism/Glycolysis ⓘ

Cell Death ⓘ

Kinase & Signal Transduction ⓘ

Transcription & Epigenetics ⓘ

DNA Damage & Repair ⓘ

Proliferation, Differentiation & Cell State ⓘ

Migration ⓘ

Angiogenesis & Vasculature ⓘ

Immune & Inflammatory Signaling ⓘ

Synaptic & Neurotransmission ⓘ

Protein Aggregation ⓘ

Hormonal & Nuclear Receptors ⓘ

Drug Metabolism & Resistance ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

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