ERK Cancer Research Results

ERK, ERK signaling: Click to Expand ⟱

Source:

Type:

MAPK3 (ERK1)
ERK proteins are kinases that activate other proteins by adding a phosphate group. An overactivation of these proteins causes the cell cycle to stop.
The extracellular signal-regulated kinase (ERK) signaling pathway is a crucial component of the mitogen-activated protein kinase (MAPK) signaling cascade, which plays a significant role in regulating various cellular processes, including proliferation, differentiation, and survival. high levels of phosphorylated ERK (p-ERK) in tumor samples may indicate active ERK signaling and could correlate with aggressive tumor behavior

EEk singaling is frequently activated and is often associated with aggressive tumor behavior, treatment resistance, and poor outcomes.

Scientific Papers found: Click to Expand⟱

2288-

AgNPs,

Silver Nanoparticle-Mediated Cellular Responses in Various Cell Lines: An in Vitro Model

Review,

Var,

*ROS↑, Several studies have reported that AgNPs induce genotoxicity and cytotoxicity in both cancer and normal cell lines
Akt↓, high ROS levels, and reduced Akt and ERK signaling.
ERK↓,
DNAdam↑, increased ROS production, leading to oxidative DNA damage and apoptosis
Ca+2↑, The damage caused to the cell membrane is due to intracellular calcium overload, and further causes ROS overproduction and mitochondrial membrane potential variation
ROS↑,
MMP↓,
Cyt‑c↑, AgNPs induce apoptosis through release of cytochrome c into the cytosol and translocation of Bax to the mitochondria, and also cause cell cycle arrest in the G1 and S phases
TumCCA↑,
DNAdam↑, main result of AgNP toxicity is direct and oxidative DNA damage, ultimately causing apoptosis
Apoptosis↑,
P53↑, AgNPs induce apoptosis in spermatogonial stem cells through increased levels of ROS; mitochondrial dysfunction; upregulation of p53 expression; pErk1/2;
p‑ERK↑,
ER Stress↑, endoplasmic reticulum (ER) stress-induced apoptosis caused by AgNPs has attracted much research interest
cl‑ATF6↑, cleavage of activating transcription factor 6 (ATF6), and upregulation of glucose-regulated protein-78 and CCAAT/enhancer-binding protein-homologous protein (CHOP/GADD153)
GRP78/BiP↑,
CHOP↑,
UPR↑, In order to protect the cells against nanoparticle-mediated toxicity, the ER rapidly responds with the unfolded protein response (UPR), an important cellular self-protection mechanism

248-

AL,

Allicin inhibits cell growth and induces apoptosis in U87MG human glioblastoma cells through an ERK-dependent pathway

in-vitro,

GBM,

U87MG

Bcl-2↓,
BAX↑,
MAPK↑,
ERK↑,
ROS↑, antioxidant prevented inhibitory effect
p38↑,
JNK↑,

235-

AL,

Allicin inhibits cell growth and induces apoptosis in U87MG human glioblastoma cells through an ERK-dependent pathway

in-vitro,

GBM,

U87MG

 90 μM

Apoptosis↑,
Bcl-2↓,
BAX↑,
MAPK↑, mechanisms involved in apoptosis include the mitochondrial pathway, activation of mitogen-activated protein kinases (MAPKs), and caspase cascade and oxidant enzyme system.
p‑ERK↑, In the present study, the level of ERK phosphorylation was increased
ROS↑, ROS are related to allicin-induced apoptosis in the U87MG cells.
eff↓, This study demonstrated that allicin-induced apoptosis was down-regulated by the antioxidant enzyme system

3272-

ALA,

Alpha-lipoic acid as a dietary supplement: Molecular mechanisms and therapeutic potential

Review,

AD,

*antiOx↑, LA has long been touted as an antioxidant,
*glucose↑, improve glucose and ascorbate handling,
*eNOS↑, increase eNOS activity, activate Phase II detoxification via the transcription factor Nrf2, and lower expression of MMP-9 and VCAM-1 through repression of NF-kappa-B.
*NRF2↑,
*MMP9↓,
*VCAM-1↓,
*NF-kB↓,
*cardioP↑, used to improve age-associated cardiovascular, cognitive, and neuromuscular deficits,
*cognitive↑,
*eff↓, The efficiency of LA uptake was also lowered by its administration in food,
*BBB↑, LA has been shown to cross the blood-brain barrier in a limited number of studies;
*IronCh↑, LA preferentially binds to Cu2+, Zn2+ and Pb2+, but cannot chelate Fe3+, while DHLA forms complexes with Cu2+, Zn2+, Pb2+, Hg2+ and Fe3+
*GSH↑, LA markedly increases intracellular glutathione (GSH),
*PKCδ↑, PKCδ, LA activates Erk1/2 [92,93], p38 MAPK [94], PI3 kinase [94], and Akt
*ERK↑,
*p38↑,
*MAPK↑,
*PI3K↑,
*Akt↑,
*PTEN↓, LA decreases the activities of Protein Tyrosine Phosphatase 1B [99], Protein Phosphatase 2A [95], and the phosphatase and tensin homolog PTEN [95],
*AMPK↑, LA activates peripheral AMPK
*GLUT4↑, stimulate GLUT4 translocation
*GLUT1↑, LA-stimulated translocation of GLUT1 and GLUT4.
*Inflam↓, LA as an anti-inflammatory agent

3539-

ALA,

Alpha-lipoic acid as a dietary supplement: Molecular mechanisms and therapeutic potential

Review,

AD,

*ROS↓, scavenges free radicals, chelates metals, and restores intracellular glutathione levels which otherwise decline with age.
*IronCh↑, LA preferentially binds to Cu2+, Zn2+ and Pb2+, but cannot chelate Fe3+, while DHLA forms complexes with Cu2+, Zn2+, Pb2+, Hg2+ and Fe3+
*GSH↑,
*antiOx↑, LA has long been touted as an antioxidant
*NRF2↑, activate Phase II detoxification via the transcription factor Nrf2
*MMP9↓, lower expression of MMP-9 and VCAM-1 through repression of NF-kappa-B.
*VCAM-1↓,
*NF-kB↓,
*cognitive↑, it has been used to improve age-associated cardiovascular, cognitive, and neuromuscular deficits, and has been implicated as a modulator of various inflammatory signaling pathways
*Inflam↓,
*BioAv↝, LA bioavailability may be dependent on multiple carrier proteins.
*BioAv↝, observed that approximately 20-40% was absorbed [
*BBB↑, LA has been shown to cross the blood-brain barrier in a limited number of studies
*H2O2∅, Neither species is active against hydrogen peroxide
*neuroP↑, chelation of iron and copper in the brain had a positive effect in the pathobiology of Alzheimer’s Disease by lowering free radical damage
*PKCδ↑, In addition to PKCδ, LA activates Erk1/2 [92, 93], p38 MAPK [94], PI3 kinase [94], and Akt [94-97].
*ERK↑,
*MAPK↑,
*PI3K↑,
*Akt↑,
*PTEN↓, LA decreases the activities of Protein Tyrosine Phosphatase 1B [99], Protein Phosphatase 2A [95], and the phosphatase and tensin homolog PTEN
*AMPK↑, LA activates peripheral AMPK
*GLUT4↑, In skeletal muscle, LA is proposed to recruit GLUT4 from its storage site in the Golgi to the sarcolemma, so that glucose uptake is stimulated by the local increase in transporter abundance.
*GlucoseCon↑,
*BP↝, Feeding LA to hypertensive rats normalized systolic blood pressure and cytosolic free Ca2+
*eff↑, Clinically, LA administration (in combination with acetyl-L-carnitine) showed some promise as an antihypertensive therapy by decreasing systolic pressure in high blood pressure patients and subjects with the metabolic syndrome
*ICAM-1↓, decreased demyelination and spinal cord expression of adhesion molecules (ICAM-1 and VCAM-1)
*VCAM-1↓,
*Dose↝, Considering the transient cellular accumulation of LA following an oral dose, which does not exceed low micromolar levels, it is entirely possible that some of the cellular effects of LA when given at supraphysiological concentrations may be not be c

3549-

ALA,

Important roles of linoleic acid and α-linolenic acid in regulating cognitive impairment and neuropsychiatric issues in metabolic-related dementia

Review,

AD,

*Inflam↓, LA and ALA attenuate neuroinflammation by modulating inflammatory signaling.
*other↝, ratio of LA to ALA in typical Western diets is reportedly 8–10:1 or higher, which is rather higher than the ideal ratio of LA to ALA (1–2:1) required to reach the maximal conversion of ALA to its longer chain PUFAs
*other↝, LA and ALA are essential PUFAs that must be obtained from dietary intake because they cannot be synthesized de novo
*neuroP↑, several studies have also suggested that lower dietary intake of LA influences AA metabolism in brain and subsequently causes progressive neurodegenerative disorders
*BioAv↝, LA cannot be synthesized in the human body
*adiP↑, study suggested that LA-rich oil consumption leads to the high levels of adiponectin in the blood [114], which could stimulate mitochondrial function in the liver and skeletal muscles for energy thermogenesis
*BBB↑, Although LA can penetrate the BBB, most of the LA that enters the brain cannot be changed into AA [48,49], and 59 % of the LA that enters the brain is broken down by fatty acid β-oxidation
*Casp6↓, In neurons, LA and ALA attenuate the activation of cleaved caspase-3/-9, p-NF-Kb and the production of TNF-a, IL-6, IL-1b, and ROS by binding GPR40 and GPR120.
*Casp9↓,
*TNF-α↓,
*IL6↓,
*IL1β↓,
*ROS↓,
*NO↓, LA reduces NO production and inducible nitric oxide synthases (iNOS) protein expression in BV-2 microglia
*iNOS↓,
*COX2↓, ALA increases antioxidant enzyme activities in the brain [182] and inhibits the activation of COX-2 in AD models
*JNK↓, ALA has also been shown to suppress the activation of c-Jun N-terminal kinases (JNKs) and p-NF-kB p65 (Ser536), which is involved in inflammatory signaling
*p‑NF-kB↓,
*Aβ↓, and to inhibit Aβ aggregation and neuronal cell necrosis
*BP↓, LA also improves blood pressure, blood triglyceride and cholesterol levels, and vascular inflammation
*memory↑, One study suggested that long-term intake of ALA enhances memory function by increasing hippocampal neuronal function through activation of cAMP response element-binding protein (CREB) [192], extracellular signal-regulated kinase (ERK), and Akt signa
*cAMP↑,
*ERK↑,
*Akt↑,
cognitive?, Furthermore, ALA administration inhibits Aβ induced neuroinflammation in the cortex and hippocampus and enhances cognitive function

3884-

Api,

Neuroprotective, Anti-Amyloidogenic and Neurotrophic Effects of Apigenin in an Alzheimer’s Disease Mouse Model

in-vivo,

AD,

double transgenic AD mice

*memory↑, Three-month oral treatment with apigenin rescued learning deficits and relieved memory retention in APP/PS1 mice.
*Aβ↓, Apigenin also showed effects affecting APP processing and preventing Aβ burden due to the down-regulation of BACE1 and β-CTF levels, the relief of Aβ deposition, and the decrease of insoluble Aβ levels.
*BACE↓, we observed BACE1 level reduction treated with apigenin.
*antiOx↑, apigenin exhibited superoxide anion scavenging effects and improved antioxidative enzyme activity of superoxide dismutase and glutathione peroxidase.
*BDNF↑, apigenin restored neurotrophic ERK/CREB/BDNF pathway in the cerebral cortex.
*p‑CREB↑, After long-term apigenin treatment, coupled with the elevation of BDNF level, enhanced phosphorylated ERK1/2 and CREB expression were detected in the cerebral cortex
*p‑ERK↑,
*ROS↓, apigenin exhibited superoxide anion scavenging effects and improved antioxidative enzyme activity of superoxide dismutase (SOD) and GSH-Px.
*SOD↑,
*GPx↑,
*neuroP↑, observations are correlated with a prospective neuroprotective, anti-amyloidogenic and neurotrophic effects in AD deficits.

4278-

ART/DHA,

Artemisinin Ameliorates the Neurotoxic Effect of 3-Nitropropionic Acid: A Possible Involvement of the ERK/BDNF/Nrf2/HO-1 Signaling Pathway

in-vivo,

NA,

Rats

*IL6↓, ART effectively suppressed neuroinflammatory (IL-6) and apoptotic markers (caspase 3 and 9), increasing BDNF levels and restoring the p-ERK1/2, Nrf2, and HO-1 expression.
*Casp3↓,
*Casp9↓,
*BDNF↑,
*ERK↑,
*NRF2↑,
*HO-1↑,
*neuroP↑, ART could exert its neuroprotective effect via antioxidant, anti-inflammatory, and antiapoptotic properties with a possible involvement of the ERK/BDNF/Nrf2/HO-1 pathway.
*antiOx↑,
*Inflam↓,

3163-

Ash,

Rad,

Withaferin A, a steroidal lactone, selectively protects normal lymphocytes against ionizing radiation induced apoptosis and genotoxicity via activation of ERK/Nrf-2/HO-1 axis

*radioP↑, Withaferin A (WA) protected only normal lymphocytes, but not cancer cells, against IR-induced apoptosis
selectivity↑,
*Casp3↓, WA treatment led to significant inhibition of IR-induced caspase-3 activation and decreased IR-induced DNA damage to lymphocytes and bone-marrow cells.
*DNAdam↓,
*ROS↓, WA reduced intracellular ROS and GSH levels
*GSH↓,
*NRF2↑, WA induced pro-survival transcription factor, Nrf-2, and expression of cytoprotective genes HO-1, catalase, SOD, peroxiredoxin-2 via ERK.
*HO-1↑,
*Catalase↑,
*SOD↑,
*Prx↑,
*ERK↑, Activated ERK promotes the nuclear translocation and activity of Nrf2

4276-

BA,

Baicalin Attenuates Oxygen–Glucose Deprivation/Reoxygenation–Induced Injury by Modulating the BDNF-TrkB/PI3K/Akt and MAPK/Erk1/2 Signaling Axes in Neuron–Astrocyte Cocultures

in-vivo,

Stroke,

Newborn Sprague–Dawley (SD) rats

*BDNF↑, has been indicated to protect neurons by promoting brain-derived neurotrophic factor (BDNF).
*neuroP↑, neuroprotective mechanisms of baicalin against oxygen–glucose deprivation/reoxygenation
*TrkB↑, baicalin significantly increased the expressions of TrkB, PI3K/AKT, and MAPK/ERK.
*PI3K↑,
*Akt↑,
*MAPK↑,
*ERK↑,
*NO↓, elevation of NO and MDA was significantly attenuated by BCL treatment.
*MDA↓,
*SOD↑, BCL treatment increased the expression level of SOD
*TNF-α↓, OGD/R treatment significantly increased the expression levels of TNF-α, IL-1β, and IL-6 (p < 0.01). Compared with that in the OGD/R group, BCL robustly reduced the release of inflammatory cytokines
*IL1β↓,
*IL6?,

2480-

Ba,

Inhibition of 12/15 lipoxygenase by baicalein reduces myocardial ischemia/reperfusion injury via modulation of multiple signaling pathways

in-vivo,

Stroke,

rat

*12LOX↓, administration of 12/15-LOX inhibitor, baicalein, significantly attenuated myocardial infarct size induced by I/R injury
*ROS↓, baicalein treatment significantly inhibited cardiomyocyte apoptosis, inflammatory responses and oxidative stress in the heart after I/R injury
*ERK↑, mechanisms underlying these effects were associated with the activation of ERK1/2 and AKT pathways and inhibition of activation of p38 MAPK, JNK1/2, and NF-kB/p65 pathways in the I/R-treated hearts
*Akt↑,
*p38↓,
*JNK↓,
*NF-kB↓,
*cardioP↑, Baicalein inhibits cardiac injury and inflammation

2624-

Ba,

Baicalein inhibition of hydrogen peroxide-induced apoptosis via ROS-dependent heme oxygenase 1 gene expression

in-vitro,

Nor,

RAW264.7

*HO-1↑, In the present study, baicalein (BE) but not its glycoside, baicalin (BI), induced heme oxygenase-1 (HO-1) gene expression at both the mRNA and protein levels
*ERK↑, BE induction of HO-1 gene expression via activation of ERKs in macrophages
*ROS↓, HO-1 protein indeed participates in BE's protection against H2O2-induced cytotoxicity via reducing ROS production
*eff↑, BE, but not BI, protection of RAW264.7 cells from H2O2-induced apoptosis
*MMP↑, BE inhibits H2O2-induced reduction of the mitochondrial membrane potential in RAW264.7 cell
*Cyt‑c∅, the release of cytochrome c from mitochondria to the cytosol was detected in H2O2-treated macrophages, and this was blocked by the addition of BE but not BI.

2598-

Ba,

Baicalein inhibits melanogenesis through activation of the ERK signaling pathway

in-vitro,

Melanoma,

B16-F10

other↓, Baicalein significantly inhibited melanin synthesis in a concentration-dependent manner without cytotoxicity
other?, Tyrosinase activity was also reduced.
ERK↑, Western blotting showed that baicalein induced ERK activation

1382-

BBR,

Berberine increases the expression of cytokines and proteins linked to apoptosis in human melanoma cells

in-vitro,

Melanoma,

SK-MEL-28

50 μM BBR treatment for 24 h

Apoptosis↑,
necrosis↑,
DNAdam↑, increase in the DNA damage index
TumCCA↑, G1/G0 phase
ROS↑, The alcaloid increased (****p < 0.001) ROS production compared to untreated controls with an increase in activated caspase 3 and phosphorylated p53 protein levels
Casp3↑,
p‑P53↑,
ERK↑, BBR significantly enhanced ERK as well as both pro- and anti-inflammatory cytokine expression compared to untreated controls.

2690-

BBR,

Berberine Differentially Modulates the Activities of ERK, p38 MAPK, and JNK to Suppress Th17 and Th1 T Cell Differentiation in Type 1 Diabetic Mice

in-vivo,

Diabetic,

berberine (Sigma, 200 mg/kg body weight), by gavage, daily for 2 weeks

11-week-old female NOD mice

*Inflam↓, Recent studies suggested that berberine has many beneficial biological effects, including anti-inflammation.
*Th17↓, Here we reported that 2 weeks of oral administration of berberine prevented the progression of type 1 diabetes in half of the NOD mice and decreased Th17 and Th1 cytokine secretion.
*Th1 response↓,
*ERK↑, berberine inhibited Th17 differentiation by activating ERK1/2 and inhibited Th1 differentiation by inhibiting p38 MAPK and JNK activation.
*p38↓,
*JNK↓,
*STAT1↓, Berberine down-regulated the activity of STAT1 and STAT4 through the suppression of p38 MAPK and JNK activation,
*STAT4↓,
*MAPK↓,

2691-

BBR,

Berberine induces FasL-related apoptosis through p38 activation in KB human oral cancer cells

in-vitro,

Oral,

tumCV↓, viability of KB cells was found to decrease significantly in the presence of berberine in a dose-dependent manner.
DNAdam↑, berberine induced the fragmentation of genomic DNA, changes in cell morphology, and nuclear condensation.
Casp3↑, caspase-3 and -7 activation, and an increase in apoptosis were observed.
Casp7↑,
FasL↑, Berberine was also found to upregulate significantly the expression of the death receptor ligand, FasL
Casp8↑, triggered the activation of pro-apoptotic factors such as caspase-8, -9 and -3 and poly(ADP-ribose) polymerase (PARP).
Casp9↑,
PARP↑,
BAX↑, Bax, Bad and Apaf-1 were also significantly upregulated by berberine.
BAD↑,
APAF1↑,
MMP2↓, We also found that berberine-induced migration suppression was mediated by downregulation of MMP-2 and MMP-9 through phosphorylation of p38 MAPK.
MMP9↓,
p‑p38↑, This suggests that berberine-induced activation of the p38 and ERK1/2 MAPK pathways is the principal pathway involved in the apoptosis mediated by berberine in KB cells.
ERK↑,
MAPK↑,

3678-

BBR,

Network pharmacology study on the mechanism of berberine in Alzheimer’s disease model

Review,

AD,

*APP↓, BBR were decreased in the mRNA and protein expression of APP and presenilin 1 while PPARG was increased with a reduction in the NF-κB pathway.
*PPARγ↑, upregulated PPARG with decreasing its downstream NF-ΚB pathway
*NF-kB↓,
*Aβ↓, BBR played a protective role in the AD mice model via blocking APP processing and amyloid plaque formation.
*cognitive↑, berberine significantly reduced amyloid accumulation and improved cognitive impairment in APP/PS1 mice
*antiOx↑, via anti-oxidative stress, anti-neuroinflammation, inhibition of neuronal cell apoptosis, etc
*Inflam↓,
*Apoptosis↓,
*BioAv↑, BBR was found to be metabolized to dihydro-berberine by intestinal bacteria, whose bioavailability was five times higher than that of BBR
*BioAv↝, oral bioavailability (OB, >30%),
*BBB↑, blood-brain barrier (BBB, >0.3)
*motorD↑, BBR treated 5×FAD mice ameliorated their behavior activity including in locomotor activity and cognitive function compared to control.
*NRF2↑, BBR enhanced cellular antioxidant capacity, regulated antioxidant-related pathways such as Nrf2 and HO-1, and thereby reduced oxidative stress damage
*HO-1↑,
*ROS↓,
*p‑Akt↑, BBR significantly increased the phosphorylation levels of AKT and ERK
*p‑ERK↑,

3680-

BBR,

Network pharmacology reveals that Berberine may function against Alzheimer’s disease via the AKT signaling pathway

in-vivo,

AD,

3 × Tg AD mice

*Akt↑, Akt1 mRNA expression levels were significantly decreased in AD mice and significantly increased after BBR treatment (p < 0.05).
*neuroP↑, BBR may exert a neuroprotective effect by modulating the ERK and AKT signaling pathways.
*p‑ERK↑, Besides, AKT and ERK phosphorylation decreased in the model group, and BBR significantly increased their phosphorylation levels.
*Aβ↓, BBR has therapeutic potential in the treatment of AD by targeting amyloid beta plaques, neurofibrillary tangles, neuroinflammation, and oxidative stress
*Inflam↓,
*ROS↓,
*BioAv↑, oral bioavailability (OB) = 36.86%, drug-likeness (DL) = 0.78,
*BBB↑, blood brain barrier (BBB) = 0.57,
*Half-Life↝, half-life (HL) = 6.57. BBR half-life (t1/2) is in the mid-elimination group.
*memory↑, BBR improves the performance of memory and recognition tasks in AD mice
*cognitive↑,
*HSP90↑, Among the core targets, Akt1 (t = −5.01, p = 0.002), Hsp90aa1 (t = −3.66, p = 0.011), Hras (t = −2.99, p = 0.024) and Igf1 (t = 3.75, p = 0.019) mRNA levels were significantly increased after BBR treatment
*APP↓, BBR reduces Aβ levels by modulating APP processing and ameliorates Aβ pathology by inhibiting the mTOR/p70S6K signaling pathway
*mTOR↓,
*P70S6K↓,
*CD31↑, it promotes the formation of brain microvessels by enhancing CD31, VEGF, N-cadherin, Ang-1 and inhibits neuronal apoptosis (Ye et al., 2021).
*VEGF↑,
*N-cadherin↑,
*Apoptosis↓,

5482-

BM,

Bacopa monnieri protects SH-SY5Y cells against tert-Butyl hydroperoxide-induced cell death via the ERK and PI3K pathways

in-vitro,

Nor,

*neuroP↑, The neuroprotective effect of BM was evaluated
*ERK↑, BM by activation of ERK/MAPK and PI3K/Akt signaling pathways protects SH-SY5Y cells from TBHP-induced cell death.
*Akt↑,
*MAPK↑,
*PI3K↑,
*Inflam↓, Mechanistically, BM has been reported to have anti-inflammatory, anti-depressant and antioxidant effects9–12
antiOx↑, enhancement of antioxidant enzymes

5693-

BRU,

Brusatol provokes a rapid and transient inhibition of Nrf2 signaling and sensitizes mammalian cells to chemical toxicity-implications for therapeutic targeting of Nrf2

in-vivo,

HCC,

mouse Hepa-1c1c7 hepatoma cells

NRF2↓, we show that brusatol provokes a rapid and transient depletion of Nrf2 protein
eff↑, brusatol is capable of sensitizing mammalian cells to chemical stress.
p‑MAPK↑, brusatol provoked a rapid increase in the phosphorylation of p38 MAPK, AKT, ERK1/2, and JNK1/2 in parallel with depletion of Nrf2
p‑Akt↑,
p‑ERK↑,
p‑JNK↑,

1651-

CA,

PBG,

Caffeic acid and its derivatives as potential modulators of oncogenic molecular pathways: New hope in the fight against cancer

Review,

Var,

Apoptosis↑,
TumCCA↓, CAPE (1-80 uM) can stimulate apoptosis and cell cycle arrest (G1 phase
TumCMig↓,
TumMeta↓,
ChemoSen↑,
eff↑, Nanoparticles promote therapeutic effect of CA and CAPE in reducing cancer cell malignancy.
eff↑, improve capacity of CA and CAPE in cancer suppression, it has been co-administered with other anti-tumor compounds such as gallic acid
eff↓, Currently, solvent extraction is utilized by methanol and ethyl acetate combination at high temperatures. However, a low amount of CA is yielded via this pathway
eff↝, Decyl CA (DCA) is a novel derivative of CA but its role in affecting colorectal cancer has not been completely understood.
Dose∅, The CAPE administration (0-60 uM) induces both autophagy and apoptosis in C6 glioma cells.
AMPK↑, CAPE induces autophagy via AMPK upregulation.
p62↓, CAPE can induce autophagy via p62 down-regulation and LC3-II upregulation
LC3II↑,
Ca+2↑, CA (0-1000 uM) enhances Ca2+ accumulation in cells in a concentration-dependent manner
Bax:Bcl2↑, CA can promote Bax/Bcl-2 ratio i
CDK4↑, The administration of CAPE (1–80 μM) can stimulate apoptosis and cell cycle arrest (G1 phase) via upregulation of Bax, CDK4, CDK6 and Rb
CDK6↑,
RB1↑,
EMT↓, CAPE has demonstrated high potential in inhibiting EMT in nasopharyngeal caner via enhancing E-cadherin levels, and reducing vimentin and β-catenin levels.
E-cadherin↑,
Vim↓,
β-catenin/ZEB1↓,
NF-kB↓,
angioG↑, CAPE (0.01-1ug/ml) inhibited angiogenesis via VEGF down-regulation
VEGF↓,
TSP-1↑, and furthermore, CAPE is capable of increasing TSP-1 levels
MMP9↓, CAPE was found to reduce MMP-9 expression
MMP2↓, CAPE can also down-regulate MMP-2
ChemoSen↑, role of CA and its derivatives in enhancing therapy sensitivity of cancer cells.
eff↑, CA administration (100 uM) alone or its combination with metformin (10 mM) can induce AMPK signaling
ROS↑, CA can promote ROS levels to induce cell death in human squamous cell carcinoma
CSCs↓, CA can reduce self-renewal capacity of CSCs and their migratory ability in vitro and in vivo.
Fas↑, CAPE (0-100 uM) is capable of inducing Fas signaling to promote p53 expression, leading to apoptotic cell death via Bax and caspase activation
P53↑,
BAX↑,
Casp↑,
β-catenin/ZEB1↓, anti-tumor activity of CAPE is mediated via reducing β-catenin levels
NDRG1↑, CAPE (30 uM) can promote NDRG1 expression via MAPK activation and down-regulation of STAT3
STAT3↓,
MAPK↑, CAPE stimulates mitogen-activated protein kinase (MAPK) and ERK
ERK↑,
eff↑, Res, thymoquinone and CAPE mediate lung tumor cell death via Bax upregulation and Bcl-2 down-regulation.
eff↑, co-administration of CA (100 Î¼M) and metformin (10 mM) is of interest in cervical squamous cell carcinoma therapy.
eff↑, in addition to CA, propolis contains other agents such as chrysin, p-coumaric acid and ferulic acid that are beneficial in tumor suppression.

6010-

CGA,

The Biological Activity Mechanism of Chlorogenic Acid and Its Applications in Food Industry: A Review

Review,

Nor,

*antiOx↑, mainly shown as anti-oxidant, liver and kidney protection, anti-bacterial, anti-tumor, regulation of glucose metabolism and lipid metabolism, anti-inflammatory, protection of the nervous system,
*hepatoP↑,
*RenoP↑,
AntiTum↑,
*glucose↝,
*Inflam↓,
*neuroP↑,
*ROS↓, ↓Active oxygen (ROS) , ↓Keap1,↑Nrf2, ↑SOD, ↑CAT, ↑Glutathione Peroxidase (GSH-Px), ↑Glutathione (GSH), ↓MDA
*Keap1↓,
*NRF2↑,
*SOD↑,
*Catalase↑,
*GPx↑,
*GSH↑,
*MDA↓,
*p‑ERK↑, ↑ERK1/2 phosphorylation
*GRP78/BiP↑, ↑Glucose regulatory protein 78 (GRP78)
*CHOP↑, ↑C/EBP homologous protein (CHOP)
*GRP94↑, ↑Glucose Regulatory Protein 94 (GRP94)
*Casp3↓, ↓Caspase-9/Caspase-3
*Casp9↓,
*HGF/c-Met↑, ↑Hepatocyte Growth Factor (HGF)
*TNF-α↓, ↓Tumor Necrosis Factor-α (TNF-α)/Interferonγ (IFN-γ)
*TLR4↓, ↓TLR4
*MAPK↓, ↓MAPK signal pathway
*IL1β↓, ↓Interleukin 1β (IL-1β)/Interleukin 6 (IL-6)
*iNOS↓, ↓Inducible Nitric Oxide Synthase (iNOS)
TCA↓, ↓Tricarboxylic acid cycle (TCA) ↓Glycolysis
Glycolysis↓,
Bcl-2↓, ↓Anti-apoptotic gene Bcl-2/Bcl-XL
BAX↑, ↑Pro-apoptotic gene Bax/Bcl-XS/Bad
MAPK↑, ↑p38 mitogen-activated protein kinase (p38 MAPK)
JNK↑, ↑c-Jun N-terminal Kinase (JNK)
CSCs↓, ↓Stem cell marker genes Nanog, POU5F1, Sox2, CD44, Oct4
Nanog↓,
SOX2↓,
CD44↓,
OCT4↓,
P53↑, ↑P53
P21↑, ↑p21
*SOD1↑, ↑CuZnSOD (SOD1)/MnSOD (SOD2)
*AGEs↓, ↓Glycosylation end products (AGEs)
*GLUT2↑, ↑Glucose Transporter 2 (GLUT2)
*HDL↑, ↑High-density lipoprotein (HDL)
*Fas↓, ↓Fatty acid synthase (FAS)
*HMG-CoA↓, ↓β-hydroxy-β-methylglutamyl-CoA (HMG-CoA) reductase
*NF-kB↓, ↑NF-κB signaling pathway
*HO-1↓, ↑Nrf2/HO-1 signaling pathway
*COX2↓, ↓Cyclooxygenase-2 (COX-2)
*TLR4↓, ↓Toll-like receptor 4 (TLR4)
*BioAv↑, One route may be immediate absorption in the stomach or upper gastrointestinal tract, and the other route may be slowly absorbed throughout the small intestine.
*BioAv↝, It indicates that the bioavailability of CGA is closely related to the metabolic capacity of the organism's gut flora
TumCP↓, CGA also inhibits the proliferation, migration, and invasion of cancer cells.
TumCMig↓,
TumCI↓,

2795-

CHr,

Combination of chrysin and cisplatin promotes the apoptosis of Hep G2 cells by up-regulating p53

in-vitro,

Liver,

HepG2

ChemoSen↑, combination chrysin and cisplatin significantly enhanced the apoptosis of Hep G2 cancer cells
P53↑, chrysin and cisplatin increased the phosphorylation and accumulation of p53 through activating ERK1/2 in Hep G2 cells
ERK↑,
BAX↑, which led to the overexpression of the pro-apoptotic proteins Bax and DR5 and the inhibition of the anti-apoptotic protein Bcl-2.
DR5↑,
Bcl-2↓,
Casp8↑, chrysin and cisplatin promoted both extrinsic apoptosis by activating caspase-8 and intrinsic apoptosis by increasing the release of cytochrome c and activating caspase-9 in Hep G2 cells
Cyt‑c↑,
Casp9↑,

2791-

CHr,

Chrysin attenuates progression of ovarian cancer cells by regulating signaling cascades and mitochondrial dysfunction

in-vitro,

Ovarian,

OV90

TumCP↓, chrysin inhibited ovarian cancer cell proliferation and induced cell death by increasing reactive oxygen species (ROS) production and cytoplasmic Ca2+ levels as well as inducing loss of mitochondrial membrane potential (MMP).
TumCD↑,
ROS↑,
Ca+2↑,
MMP↓,
MAPK↑, chrysin activated mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K)/AKT pathways in ES2 and OV90 cells in concentration-response experiments
PI3K↑, results indicate that the chrysin-induced activation of PI3K and MAPK signaling molecules, which induced apoptosis,
p‑Akt↑, Chrysin stimulated the phosphorylation of AKT and P70S6K proteins in both ES2 and OV90 cells compared to the untreated control cell
PCNA↓, treatment with chrysin attenuated the abundant expression of PCNA protein in both ES2 and OV90 cells
p‑p70S6↑,
p‑ERK↑, chrysin activated the phospho-ERK1/2, p38, and JNK proteins as members of the MAPK pathway in the ovarian cancer cells
p38↑,
JNK↑,
DNAdam↑, stimulates apoptotic events in prostate cancer cells by the accumulation of DNA fragmentation, an increase in the population of cells in the sub-G1 phase of the cell cycle
TumCCA↑,
chemoP↑, combination therapy with chrysin enhances the therapeutic effect of the chemotherapeutic agent, docetaxel, in lung cancer by reducing its adverse effects

1980-

CUR,

Rad,

Thioredoxin reductase-1 (TxnRd1) mediates curcumin-induced radiosensitization of squamous carcinoma cells

in-vitro,

Cerv,

HeLa

10 µM

in-vitro,

Laryn,

FaDu

10 µM

selectivity↑, previously demonstrated that curcumin radiosensitizes cervical tumor cells without increasing the cytotoxic effects of radiation on normal human fibroblasts
RadioS↑,
TrxR↓, inhibitory activity of curcumin on the anti-oxidant enzyme Thioredoxin Reductase-1 (TxnRd1) is required for curcumin-mediated radiosensitization of squamous carcinoma cells
ROS↑, induced reactive oxygen species
ERK↑, sustained ERK1/2 activation
Dose∅, Curcumin treatment resulted in a dose-dependent decrease in TxnRd activity with an IC50 of approximately 10 µM in both cell lines
cl‑PARP↑, curcumin induced a robust increase in cleaved PARP

4175-

CUR,

Effects of curcumin on learning and memory deficits, BDNF, and ERK protein expression in rats exposed to chronic unpredictable stress

in-vivo,

NA,

CUS rats

*BDNF↑, CUS reduced hippocampal BDNF and ERK levels, while curcumin effectively reversed these alterations
*ERK↑, related to its aptitude to promote BDNF and ERK in the hippocampus.

144-

CUR,

Bical,

Combination of curcumin and bicalutamide enhanced the growth inhibition of androgen-independent prostate cancer cells through SAPK/JNK and MEK/ERK1/2-mediated targeting NF-κB/p65 and MUC1-C

in-vitro,

Pca,

PC3

 androgen-independent prostate cancer cells

in-vitro,

PC,

DU145

in-vitro,

PC,

LNCaP

p‑ERK↑, ERK1/2
p‑JNK↓, phosphorylation
MUC1↓, MUC1-C protein expression
p65↓,
AR↓, bicalutamide, an androgen receptor antagonist, inhibited cell growth in dose- and time-dependent fashion in PC3 and LNCaP cells.
TumCG↓,
MEK↑, curcumin inhibits the growth of androgen-independent prostate cancer cells through MEK/ERK1/2 and SAPK/JNK-mediated inhibition of p65, followed by reducing expression of MUC1-C protein.
SAPK↑, through activation of MEK/ERK/12 and SAPK/JNK

463-

CUR,

Curcumin induces autophagic cell death in human thyroid cancer cells

in-vitro,

Thyroid,

10, 12.5, 20, 25, 30, 40 and 50 µM, 24 and 72 h

in-vitro,

Thyroid,

FTC-133

in-vitro,

Thyroid,

BCPAP

in-vitro,

Thyroid,

8505C

TumAuto↑,
LC3II↑,
Beclin-1↑,
p‑p38↑,
p‑JNK↑,
p‑ERK↑, p-ERK1/2
p62↓,
p‑PDK1↓,
p‑Akt↓,
p‑p70S6↓,
p‑PIK3R1↓,
p‑S6↓,
p‑4E-BP1↓,

462-

CUR,

Curcumin promotes cancer-associated fibroblasts apoptosis via ROS-mediated endoplasmic reticulum stress

in-vitro,

Pca,

PC3

10, 20 and 30 μM, 8, 12 and 24 h

Bcl-2↓,
MMP↓,
cl‑Casp3↑,
BAX↑,
BIM↑,
p‑PARP↑,
PUMA↑,
p‑P53↑,
ROS↑,
p‑ERK↑,
p‑eIF2α↑,
CHOP↑,
ATF4↑,

2821-

CUR,

Antioxidant curcumin induces oxidative stress to kill tumor cells (Review)

Review,

Var,

*antiOx↑, Curcumin is a plant polyphenol in turmeric root and a potent antioxidant
*NRF2↑, regulation by nuclear factor erythroid 2-related factor 2, thereby suppressing reactive oxygen species (ROS) and exerting anti-inflammatory, anti-infective and other pharmacological effects
*ROS↓,
*Inflam↓,
ROS↑, Of note, curcumin induces oxidative stress in tumors. curcumin-induced accumulation of ROS in tumors to kill tumor cells has been noted in several studies
p‑ERK↑, Curcumin promoted ERK/JNK phosphorylation, causing elevated ROS levels and triggering mitochondria-dependent apoptosis
ER Stress↑, Curcumin triggered disturbances in Ca2+ homeostasis, leading to endoplasmic reticulum stress, mitochondrial damage and apoptosis
mtDam↑,
Apoptosis↑,
Akt↓, Curcumin inhibited the AKT/mTOR/p70S6K signaling pathway
mTOR↓,
HO-1↑, Curcumin-induced HO-1 overexpression led to a disturbed intracellular iron distribution and triggered the Fenton reaction
Fenton↑,
GSH↓, Non-small cell lung cancer: Curcumin induced a decrease in GSH and an increase in ROS levels and iron accumulation
Iron↑,
p‑JNK↑, Curcumin causes mitochondrial damage by promoting phosphorylation of ERK and JNK, resulting in the increased release of ROS and cytochrome c into the cytoplasm, thereby triggering a mitochondrion-dependent pathway of apoptosis
Cyt‑c↑,
ATF6↑, thyroid cancer with curcumin, both activating transcription factor (ATF) 6 and the ER stress marker C/EBP homologous protein (CHOP) were activated by curcumin and Ca2+-ATPase activity was also affected.
CHOP↑,

670-

EGCG,

Epigallocatechin-3-gallate and its nanoformulation in cervical cancer therapy: the role of genes, MicroRNA and DNA methylation patterns

Review,

NA,

TumCCA↑, EGCG promoted G1 phase arrest
P53↑,
ERK↓, EGCG inactivated ERK1/2 protein kinases
EGFR↓,
p‑ERK↑,
VEGF↓,
Hif1a↓,
miR-203↓, in CA33 cells only
miR-210↑,

1303-

EGCG,

(-)-Epigallocatechin-3-gallate induces apoptosis in human endometrial adenocarcinoma cells via ROS generation and p38 MAP kinase activation

in-vitro,

EC,

TumCP↓,
ER-α36↓,
cycD1/CCND1↓,
ERK↑,
Jun↓,
BAX↑,
Bcl-2↓,
cl‑Casp3↑,
ROS↑,
p38↑,

1654-

FA,

Molecular mechanism of ferulic acid and its derivatives in tumor progression

Review,

Var,

AntiCan↑, FA has anti-inflammatory, analgesic, anti-radiation, and immune-enhancing effects and also shows anticancer activity,
Inflam↓,
RadioS↑,
ROS↑, FA can cause mitochondrial apoptosis by inducing the generation of intracellular reactive oxygen species (ROS)
Apoptosis↑,
TumCCA↑, G0/G1 phase
TumCMig↑, inducing autophagy; inhibiting cell migration, invasion, and angiogenesis
TumCI↓,
angioG↓,
ChemoSen↑, synergistically improving the efficacy of chemotherapy drugs and reducing adverse reactions.
ChemoSideEff↓,
P53↑, FA could increase the expression level of p53 in MIA PaCa-2 pancreatic cancer cells
cycD1/CCND1↓, while reducing the expression levels of cyclin D1 and cyclin-dependent kinase (CDK) 4/6.
CDK4↓,
CDK6↓,
TumW↓, FA treatment was found to reduce tumor weight in a dose-dependent manner, increase miR-34a expression, downregulate Bcl-2 protein expression, and upregulate caspase-3 protein expression
miR-34a↑,
Bcl-2↓,
Casp3↑,
BAX↑,
β-catenin/ZEB1↓, isoferulic acid dose-dependently downregulated the expression of β-catenin and MYC proto-oncogene (c-Myc), inducing apoptosis
cMyc↓,
Bax:Bcl2↑, FXS-3 can inhibit the activity of A549 cells by upregulating the Bax/Bcl-2 ratio
SOD↓, After treatment with FA, Cao et al. [40] observed an increase in ROS production and a decrease in superoxide dismutase activity and glutathione content in EC-1 and TE-4 oesophageal cancer cells
GSH↓,
LDH↓, FA could promote the release of lactate dehydrogenase (LDH)
ERK↑, A can activate the ERK1/2 pathway
eff↑, conjugated zinc oxide nanoparticles with FA (ZnONPs-FA) to act on hepatoma Huh-7 and HepG2 cells. The results showed that ZnONPs-FA could induce oxidative DNA damage and apoptosis by inducing ROS production.
JAK2↓, by inhibiting the JAK2/STAT6 immune signaling pathway
STAT6↓,
NF-kB↓, thus inhibiting the activation of NF-κB
PYCR1↓, FA can target PYCR1 and inhibit its enzyme activity in a concentration-dependent manner.
PI3K↓, FA inhibits the activation of the PI3K/AKT pathway
Akt↓,
mTOR↓, FA could significantly reduce the expression level of mTOR mRNA and Ki-67 protein in A549 lung cancer graft tissue
Ki-67↓,
VEGF↓,
FGFR1↓, FA is a novel FGFR1 inhibitor
EMT↓, FA can inhibit EMT
CAIX↓, selectively inhibit CAIX
LC3II↑, Autophagy vacuoles and increased LC3-II and p62 autophagy proteins were observed after treatment with this compound
p62↑,
PKM2↓, FA could inhibit the expression of PKM2 and block aerobic glycolysis
Glycolysis↓,
*BioAv↓, FA has poor solubility in water and a poor ability to pass through biological barriers [118]; therefore, the extent to which it is metabolized in vivo after oral administration is largely unknown

3712-

FA,

Ferulic Acid: A Hope for Alzheimer’s Disease Therapy from Plants

Review,

AD,

*antiOx↑, Ferulic acid (FA) is an antioxidant naturally present in plant cell walls with anti-inflammatory activities and it is able to act as a free radical scavenger.
*Inflam↓,
*ROS↓,
*Aβ↓, “FA could prevent the development of AD, not only through scavenging reactive oxygen species, but also through direct inhibition of the deposition of fibrils in the brain”
*HO-1↑, FA plays a cytoprotective role through the up-regulation of enzymes such as heme oxygenase-1, heat shock protein 70, extracellular signal-regulated kinase (ERK) 1/2, and serine/threonine kinase (Akt).
*HSP70/HSPA5↑,
*ERK↑,
*Akt↑,
*iNOS↓, , FA inhibits the expression and/or activity of cytotoxic enzymes, including inducible nitric oxide synthase, caspases, and cyclooxygenase-2
*COX2↓,
*cardioP↑, treatment of several age-related diseases, such as neurodegenerative disorders, cardiovascular diseases, diabetes, and cancer
*memory↑, reported that the long-term administration of FA to mice protected against learning and memory deficits induced by centrally administered β-amyloid
*IL2↓, FA is able to significantly reduce the interleukin-1β (IL-1β) cortical levels
*cognitive↑, FA reversed behavioral impairment, including hyperactivity, object recognition, spatial working, and reference memory.
*APP↓, it reduced amyloidogenic APP metabolism by modulation of β-secretase, attenuated neuroinflammation, and stabilized oxidative stress.
*SOD↑, superoxide dismutase (SOD), catalase (CAT) ERK 1/2, and Akt [95].
*Catalase↑,
*Akt↑,
*BioAv↑, A good strategy to increase the bioavailability and the cytoprotective effect of compounds such as FA is the formulation of new nanoparticles.

2850-

FIS,

Fisetin regulates TPA-induced breast Cancer cell invasion by suppressing matrix metalloproteinase-9 activation via the PKC/ROS/MAPK pathways

in-vitro,

BC,

MCF-7

TumCI↓, Fisetin significantly attenuated TPA-induced cell invasion in MCF-7 human breast cancer cells, and was found to inhibit the activation of the PKCα/ROS/ERK1/2 and p38 MAPK signaling pathways.
PKCδ↓,
ROS↓,
ERK↑,
p38↓,
NF-kB↓, reduced NF-κB activation
MMP9↓, reduced TPA activation of PKCα/ROS/ERK1/2 and p38 MAPK signals, ultimately leading to the downregulation of MMP-9 expression.

2825-

FIS,

Exploring the molecular targets of dietary flavonoid fisetin in cancer

Review,

Var,

*Inflam↓, present in fruits and vegetables such as strawberries, apple, cucumber, persimmon, grape and onion, was shown to possess anti-microbial, anti-inflammatory, anti-oxidant
*antiOx↓, fisetin possesses stronger oxidant inhibitory activity than well-known potent antioxidants like morin and myricetin.
*ERK↑, inducing extracellular signal-regulated kinase1/2 (ERK)/c-myc phosphorylation, nuclear NF-E2-related factor-2 (Nrf2), glutamate cystine ligase and glutathione (GSH) levels
*p‑cMyc↑,
*NRF2↑,
*GSH↑,
*HO-1↑, activate Nrf2 mediated induction of hemeoxygenase-1 (HO-1) important for cell survival
mTOR↓, in our studies on fisetin in non-small lung cancer cells, we found that fisetin acts as a dual inhibitor PI3K/Akt and mTOR pathways
PI3K↓,
Akt↓,
TumCCA↑, fisetin treatment to LNCaP cells resulted in G1-phase arrest accompanied with decrease in cyclins D1, D2 and E and their activating partner CDKs 2, 4 and 6 with induction ofWAF1/p21 and KIP1/p27
cycD1/CCND1↓,
cycE/CCNE↓,
CDK2↓,
CDK4↓,
CDK6↓,
P21↑,
p27↑,
JNK↑, fisetin could inhibit the metastatic ability of PC-3 cells by suppressing of PI3 K/Akt and JNK signaling pathways with subsequent repression of matrix metalloproteinase-2 (MMP-2) and MMP-9
MMP2↓,
MMP9↓,
uPA↓, fisetin suppressed protein and mRNA levels of MMP-2 and urokinase-type plasminogen activator (uPA) in an ERK-dependent fashion.
NF-kB↓, decrease in the nuclear levels of NF-B, c-Fos, and c-Jun was noted in fisetin treated cells
cFos↓,
cJun↓,
E-cadherin↑, upregulation of E-cadherin and down-regulation of vimentin and N-cadherin.
Vim↓,
N-cadherin↓,
EMT↓, EMT inhibiting potential of fisetin has been reported in melanoma cells
MMP↓, The shift in mitochondrial membrane potential was accompanied by release of cytochrome c and Smac/DIABLO resulting in activation of the caspase cascade and cleavage of PARP
Cyt‑c↑,
Diablo↑,
Casp↑,
cl‑PARP↑,
P53↑, fisetin with induction of p53 protein
COX2↓, Fisetin down-regulated COX-2 and reduced the secretion of prostaglandin E2 without affecting COX-1 protein expression.
PGE2↓,
HSP70/HSPA5↓, It was shown that the induction of HSF1 target proteins, such as HSP70, HSP27 and BAG3 were inhibited in HCT-116 cells exposed to heat shock at 43 C for 1 h in the presence of fisetin
HSP27↓,
DNAdam↑, DNA fragmentation, an increase in the number of sub-G1 phase cells, mitochondrial membrane depolarization and activation of caspase-9 and caspase-3.
Casp3↑,
Casp9↑,
ROS↑, This was associated with production of intracellular ROS
AMPK↑, Fisetin induced AMPK signaling
NO↑, fisetin induced cytotoxicity and showed that fisetin induced apoptosis of leukemia cells through generation of NO and elevated Ca2+ activating the caspase
Ca+2↑,
mTORC1↓, Fisetin was shown to inhibit the mTORC1 pathway and its downstream components including p70S6 K, eIF4B and eEF2 K.
p70S6↓,
ROS↓, Others have also noted a similar decrease in ROS with fisetin treatment.
ER Stress↑, Induction of ER stress upon fisetin treatment, evident as early as 6 h, and associated with up-regulation of IRE1, XBP1s, ATF4 and GRP78, was followed by autophagy which was not sustained
IRE1↑,
ATF4↑,
GRP78/BiP↑,
eff↑, Combination of fisetin and the BRAF inhibitor sorafenib was found to be extremely effective in inhibiting the growth of BRAF-mutated human melanoma cells
eff↑, synergistic effect of fisetin and sorafenib was observed in human cervical cancer HeLa cells,
eff↑, Similarly, fisetin in combination with hesperetin induced apoptosis
RadioS↑, pretreatment with fisetin enhanced the radio-sensitivity of p53 mutant HT-29 cancer cells,
ChemoSen↑, potential of fisetin in enhancing cisplatin-induced cytotoxicity in various cancer models
Half-Life↝, intraperitoneal (ip) dose of 223 mg/kg body weight the maximum plasma concentration (2.53 ug/ml) of fisetin was reached at 15 min which started to decline with a first rapid alpha half-life of 0.09 h and a longer half-life of 3.12 h.

4250-

Flav,

Dietary Flavonoids Interaction with CREB-BDNF Pathway: An  Unconventional Approach for Comprehensive Management of Epilepsy

Review,

NA,

*ERK↑, Flavonoids are the polyphenolic compounds which lead to phosphorylation of CREB in the hippocampus, followed by increase in extracellular signal regulated kinase (ERK) and BDNF.
*BDNF↑,
*CREB↑, beneficial effects of flavonoids in cognitive and memory impairments by upregulation of CREB-BDNF pathway.

1971-

GamB,

Gambogic acid triggers vacuolization-associated cell death in cancer cells via disruption of thiol proteostasis

in-vitro,

Nor,

MCF10

in-vitro,

BC,

MDA-MB-435

1.5 μM

in-vitro,

BC,

MDA-MB-468

2.35 μM

in-vivo,

NA,

injections of saline or GA (4 or 8 mg/kg) twice

mice

Paraptosis↑, GA kills cancer cells by inducing paraptosis, a vacuolization-associated cell death.
ER Stress↑, GA-induced proteasomal inhibition was found to contribute to the ER dilation and ER stress seen in treated cancer cells
MMP↓, mitochondrial membrane depolarization.
eff↓, GA-induced paraptosis was effectively blocked by various thiol-containing antioxidants
selectivity↑, MCF-10A (normal) cells were relatively resistant to this effect of GA at doses up to 3 μM
p‑ERK↑, In cells treated with 1 μM GA, the phosphorylation levels of ERKs and JNKs were markedly increased
p‑JNK↑,
eff↓, Interestingly, the general antioxidant, N-acetylcysteine (NAC), but not the mitochondria-targeted antioxidant, Tiron19, dose-dependently blocked GA-induced cell death and vacuolation in all of the tested cancer cell lines

4302-

Gins,

Panax ginseng: A modulator of amyloid, tau pathology, and cognitive function in Alzheimer's disease

Review,

AD,

*neuroP↑, highlighting neuroprotective mechanisms, such as the inhibition of Aβ production, enhanced Aβ clearance, and suppression of tau hyperphosphorylation.
*Aβ↓,
*p‑tau↓,
*cognitive↑, Research on P. ginseng and its bioactive ginsenosides has shown potential for improving cognitive function in AD models
*eff↑, particularly pronounced effects in individuals lacking apolipoprotein ε4 allele.
*PKA↑, Upregulates the PKA/CREB signaling pathway
*CREB↑,
*BACE↓, Inhibits BACE1 activity
*ADAM10↑, Enhances the expression of ADAM10 and reduces BACE1 expression through the activation of MAPK/ERK and PI3K/AKT
*MAPK↑,
*ERK↑,
*PI3K↑,
*Akt↑,
*NRF2↑, Activates the Nrf2/Keap1 signaling pathway
*PPARγ↓, Inhibits PPARγ phosphorylation and upregulates the expression of IDE
*IDE↑,
*APP↓, downregulates the expression of BACE1 and APP
*PP2A↑, Ginsenoside Rb1 enhances PP2A levels, thereby facilitating tau dephosphorylation and reducing p-tau levels observed in animal studies
*memory↑, The 400 mg dose of ginseng extract significantly improved “Quality of Memory” and “Secondary Memory” at all post-dose time points,

4343-

H2,

Inhibitory effects of hydrogen on in vitro platelet activation and in vivo prevention of thrombosis formation

vitro+vivo,

NA,

*antiOx↑, H2 has antithrombotic effects, which may be due to its antioxidant property and subsequent inhibition of platelet activation via NO/cGMP/PKG/ERK pathway.
*AntiAg↑,
*NO↑,
*ERK↑,

2073-

HNK,

Honokiol induces apoptosis and autophagy via the ROS/ERK1/2 signaling pathway in human osteosarcoma cells in vitro and in vivo

in-vitro,

OS,

U2OS

21.5 μM

in-vivo,

NA,

40 mg/kg

TumCD↑, honokiol caused dose-dependent and time-dependent cell death in human osteosarcoma cells
TumAuto↑, death induced by honokiol were primarily autophagy and apoptosis.
Apoptosis↑,
TumCCA↑, honokiol induced G0/G1 phase arrest,
GRP78/BiP↑, elevated the levels of glucose-regulated protein (GRP)−78, an endoplasmic reticular stress (ERS)-associated protein
ROS↑, increased the production of intracellular reactive oxygen species (ROS)
eff↓, In contrast, reducing production of intracellular ROS using N-acetylcysteine, a scavenger of ROS, concurrently suppressed honokiol-induced cellular apoptosis, autophagy, and cell cycle arrest.
p‑ERK↑, honokiol stimulated phosphorylation of extracellular signal-regulated kinase (ERK)1/2.
selectivity↑, human fibroblasts showed strong resistance to HNK, the IC50 values for which were 118.9 and 71.5 μM
Ca+2↑, HNK increased intracellular Ca2+ in both HOS and U2OS cells
MMP↓, mitochondrial membrane potential (MMP) sharply decreased following HNK treatment
Casp3↑, HNK markedly activated caspase-3, caspase-9
Casp9↑,
cl‑PARP↑, led to PARP cleavage
Bcl-2↓, expression of Bcl-2, Bcl-xl, and survivin was found to be decreased
Bcl-xL↓,
survivin↓,
LC3B-II↑, HNK increased the level of LC3B-II and Atg5 in HOS and U2OS cells.
ATG5↑,
TumVol↓, HNK at doses of 40 mg/kg resulted in significant decrease in tumor volume and weight, after 7 days of drug administration
TumW↓,
ER Stress↑, ER stress can trigger ROS production through release of calcium

2869-

HNK,

Nature's neuroprotector: Honokiol and its promise for Alzheimer's and Parkinson's

Review,

AD,

Review,

Park,

*neuroP↑, neuroprotective, anti-oxidant, anti-apoptotic, neuromodulating, anti-inflammatory, and many more qualities, honokiol,
*Inflam↓,
*motorD↑, degradation of dopaminergic neurons in Parkinson's disease and improving motor function.
*Aβ↓, Alzheimer's disease, honokiol showed promise in lowering the production of amyloid-beta (Aβ) plaques, phosphorylating tau, and enhancing cognitive performance
*p‑tau↓,
*cognitive↑,
*memory↑, prevented Acetylcholinesterase activity from elevation as well as improved acetylcholine levels, and improved learning, and memory deficits via increased ERK1/2 and Akt phosphorylation
*ERK↑,
*p‑Akt↑,
*PPARγ↑, honokiol has been reported to elevate PPARγ levels in APPswe/PS1dE9 mice as PPARγ is related to ani-inflammatory
*PGC-1α↑, honokiol boosted the expression of PGC1α and PPARγ
*MMP↑, as well as reduced elevated mitochondrial membrane potential and mitochondrial ROS
*mt-ROS↓,
*SIRT3↑, Honokiol has been found as a dual SIRT-3 activator and PPAR-γ agonist that reduced oxidative stress markers within cells and changed the AMPK pathway
*IL1β↓, honokiol prevented restraint stress-induced cognitive dysfunction by reducing the hippocampus's production of IL-1β, TNF-α, glucose-regulated protein (GRP78), and C/EBP homologous protein (CHOP)
*TNF-α↓,
*GRP78/BiP↓,
*CHOP↓,
*NF-kB↓, Additionally, the neuroprotective benefits of honokiol in mice with Aβ-induced learning and memory impairment have been attributed to the inactivation of NF-κB
*GSK‐3β↓, Treatment of honokiol in PC12 cells resulted in reduced GSK-3β and induced β-catenin which effectively showed the neuroprotective and anti-oxidant effect in AD therapy
*β-catenin/ZEB1↑,
*Ca+2↓, , anti-apoptotic effect via reduced caspase 3 levels, and protected membrane injury by reduced calcium level has been investigated in PC12 cells of AD models
*AChE↓, protective effects by serving as an antioxidant, reduced AchE levels, repaired neurofibrillary tangles, reduced NF-kB which downregulates Aβ plaque
*SOD↑, fig1
*Catalase↑,
*GPx↑,

4213-

Hup,

Huperzine A-Liposomes Efficiently Improve Neural Injury in the Hippocampus of Mice with Chronic Intermittent Hypoxia

in-vivo,

NA,

CIH mice

*cognitive↑, HuA-LIP significantly ameliorated cognitive dysfunction and neuronal damage in CIH mice.
*SOD↑, HuA-LIP elevated T-SOD and GSH-Px abilities and decreased MDA content to resist oxidative stress damage induced by CIH.
*GPx↑,
*MDA↓,
*ROS↓,
*Iron↓, HuA-LIP reduced brain iron levels by downregulating TfR1, hepcidin, and FTL expression.
*TfR1/CD71↓,
*FTL↓,
*ERK↑, HuA-LIP activated the PKAα/Erk/CREB/BDNF signaling pathway and elevated MAP2, PSD95, and synaptophysin to improve synaptic plasticity.
*PKA↑,
*CREB↑,
*BDNF↑,
*PSD95↑,
*neuroP↑, HuA-LIP showed a superior performance against neuronal damage induced by CIH.

2923-

LT,

Luteolin induces apoptosis through endoplasmic reticulum stress and mitochondrial dysfunction in Neuro-2a mouse neuroblastoma cells

in-vitro,

NA,

Apoptosis↑, Luteolin induced apoptotic cell death and activation of caspase-12, -9, and -3
TumCD↑,
Casp12↑,
Casp9↑,
Casp3↑,
ER Stress↑, Luteolin also induced expression of endoplasmic reticulum (ER) stress-associated proteins, including C/EBP homologous protein (CHOP) and glucose-regulated proteins (GRP) 94 and 78, cleavage of ATF6α, and phosphorylation of eIF2α
CHOP↑,
GRP78/BiP↑,
GRP94↑,
cl‑ATF6↑,
p‑eIF2α↑,
MMP↓, rapid reduction of mitochondrial membrane potential by luteolin
JNK↓, luteolin induced activation of mitogen-activated protein kinases such as JNK, p38, and ERK
p38↑,
ERK↑,
Cyt‑c↑, cytochrome c release.

4786-

Lyco,

Anti-proliferative and apoptosis-inducing activity of lycopene against three subtypes of human breast cancer cell lines

in-vitro,

BC,

MDA-MB-468

10.3 μM

in-vitro,

BC,

MCF-7

29.9 μM

in-vitro,

BC,

SkBr3

22.8 μM

TumCP↓, dose-dependent anti-proliferative activity against these cell lines by arresting the cell cycle at the G0/G1 phase at physiologically achievable concentrations found in human plasma.
TumCCA↑,
cl‑PARP↑, demonstrable cleavage of PARP.
ERK↑, Lycopene induced strong and sustained activation of the ERK1/2, with concomitant cyclin D1 suppression and p21 upregulation in these three cell lines
cycD1/CCND1↓,
P21↓,
p‑Akt↓, lycopene inhibited the phosphorylation of Akt and its downstream molecule mTOR, followed by subsequent upregulation of proapoptotic Bax
mTOR↓,
BAX↑,
AntiCan↑, data indicate that the predominant anticancer activity of lycopene in MDA-MB-468 cells
Risk↓, Lycopene has been shown to reduce the risk of overall breast cancer more prominently than other carotenoids

2243-

MF,

Pulsed electromagnetic fields increase osteogenetic commitment of MSCs via the mTOR pathway in TNF-α mediated inflammatory conditions: an in-vitro study

in-vitro,

Nor,

mesenchymal stem cells (MSCs)

*eff↑, PEMF exposure increased cell proliferation and adhesion
*mTOR↑, PEMFs contribute to activation of the mTOR pathway via upregulation of the proteins AKT, MAPP kinase, and RRAGA, suggesting that activation of the mTOR pathway is required for PEMF-stimulated osteogenic differentiation.
*Akt↑,
*PKA↑, PEMFs increase the activity of certain kinases belonging to known intracellular signaling pathways, such as the protein kinase A (PKA) and the MAPK ERK1/2
*MAPK↑,
*ERK↑,
*BMP2↑, PEMFs stimulation also upregulates BMP2 expression in association with increased differentiation in mesenchymal stem cells (MSCs
*Diff↑,
*PKCδ↓, Decrease in PKC protein (involved on Adipogenesis)
*VEGF↑, Increase on VEGF (involved on angiogenesis)
*IL10↑, PEMF induced a significant increase of in vitro expression of IL-10 (that exerts anti-inflammatory activity)

4146-

MF,

Pulsed electromagnetic field enhances brain-derived neurotrophic factor expression through L-type voltage-gated calcium channel- and Erk-dependent signaling pathways in neonatal rat dorsal root ganglion neurons

in-vivo,

AD,

50Hz and 1mT PEMF for 2h

rat

*BDNF↑, Exposure to 50Hz and 1mT PEMF for 2h increased the level of [Ca(2+)]i and Bdnf mRNA expression
*ERK↑, indicating that Erk activation is required for PEMF-induced upregulation of BDNF expression.

527-

MF,

Effects of Fifty-Hertz Electromagnetic Fields on Granulocytic Differentiation of ATRA-Treated Acute Promyelocytic Leukemia NB4 Cells

in-vitro,

AML,

APL NB4

2mT, 50Hz

ROS↑, a significant increase in ROS levels was observed shortly after exposure to ELF-EMF
other↑, F-EMF exposure promotes ATRA-induced differentiation in APL NB4 cells and suggest the possible involvement of ROS and ERK signalling pathway in this phenomenon
p‑ERK↑, ERK1/2 phosphorylation
TumCP↓, ELF-EMF exposure decreases cellular proliferation potential

486-

MF,

mTOR Activation by PI3K/Akt and ERK Signaling in Short ELF-EMF Exposed Human Keratinocytes

in-vitro,

Nor,

HaCaT

50 Hz, 1 mT for 1 h

*mTOR↑,
*PI3K↑, HaCaT cells exposed for 1h to 50Hz/1mT showed an increased percentage of cells in the S phase, through a significantly activation of the PI3K, JNK and ERK pathways
*Akt↑,
*p‑ERK↑,
*other↑, increases in the percentage of cells in the S phase and decrease in the percentage of cells in G0/G1 phase
*p‑JNK↑,
*p‑P70S6K↑,

513-

MF,

Exposure to a specific time-varying electromagnetic field inhibits cell proliferation via cAMP and ERK signaling in cancer cells

in-vitro,

BC,

MDA-MB-231

Thomas-EMF, a low-intensity, frequency-modulated (25-6 Hz) EMF pattern

in-vitro,

BC,

MDA-MB-468

in-vitro,

BC,

MCF-7

in-vivo,

Pca,

HeLa

TumCG↓, but did not affect non-malignant cells. ****
p‑ERK↑,
cAMP⇅, changed the level

Showing Research Papers: 1 to 50 of 80
Page 1 of 2 Next

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 80

Pathway results for Effect on Cancer / Diseased Cells:

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

antiOx↓, 1, antiOx↑, 9, Catalase↑, 4, GPx↑, 4, GSH↓, 1, GSH↑, 4, H2O2∅, 1, HDL↑, 1, HO-1↓, 1, HO-1↑, 6, Iron↓, 1, Keap1↓, 1, MDA↓, 3, NRF2↑, 9, Prx↑, 1, ROS↓, 12, ROS↑, 1, mt-ROS↓, 1, SIRT3↑, 1, SOD↑, 7, SOD1↑, 1,

Metal & Cofactor Biology ⓘ

FTL↓, 1, IronCh↑, 2, TfR1/CD71↓, 1,

Mitochondria & Bioenergetics ⓘ

MMP↑, 2, PGC-1α↑, 1,

Core Metabolism/Glycolysis ⓘ

12LOX↓, 1, adiP↑, 1, AMPK↑, 2, cAMP↑, 1, p‑cMyc↑, 1, CREB↑, 3, p‑CREB↑, 1, glucose↑, 1, glucose↝, 1, GlucoseCon↑, 1, GLUT2↑, 1, HMG-CoA↓, 1, PPARγ↓, 1, PPARγ↑, 2,

Cell Death ⓘ

Akt↑, 12, p‑Akt↑, 2, Apoptosis↓, 2, BMP2↑, 1, Casp3↓, 3, Casp6↓, 1, Casp9↓, 3, Cyt‑c∅, 1, Fas↓, 1, HGF/c-Met↑, 1, iNOS↓, 3, JNK↓, 3, p‑JNK↑, 1, MAPK↓, 2, MAPK↑, 6, p38↓, 2, p38↑, 1,

Transcription & Epigenetics ⓘ

other↑, 1, other↝, 2,

Protein Folding & ER Stress ⓘ

CHOP↓, 1, CHOP↑, 1, GRP78/BiP↓, 1, GRP78/BiP↑, 1, GRP94↑, 1, HSP70/HSPA5↑, 1, HSP90↑, 1,

DNA Damage & Repair ⓘ

DNAdam↓, 1,

Proliferation, Differentiation & Cell State ⓘ

Diff↑, 1, ERK↑, 20, p‑ERK↑, 5, GSK‐3β↓, 1, mTOR↓, 1, mTOR↑, 2, P70S6K↓, 1, p‑P70S6K↑, 1, PI3K↑, 6, PTEN↓, 2, STAT1↓, 1, STAT4↓, 1,

Migration ⓘ

AntiAg↑, 1, APP↓, 4, Ca+2↓, 1, CD31↑, 1, MMP9↓, 2, N-cadherin↑, 1, PKA↑, 3, PKCδ↓, 1, PKCδ↑, 2, VCAM-1↓, 3, β-catenin/ZEB1↑, 1,

Angiogenesis & Vasculature ⓘ

eNOS↑, 1, NO↓, 2, NO↑, 1, VEGF↑, 2,

Barriers & Transport ⓘ

BBB↑, 5, GLUT1↑, 1, GLUT4↑, 2,

Immune & Inflammatory Signaling ⓘ

COX2↓, 3, ICAM-1↓, 1, IL10↑, 1, IL1β↓, 4, IL2↓, 1, IL6?, 1, IL6↓, 2, Inflam↓, 13, NF-kB↓, 6, p‑NF-kB↓, 1, Th1 response↓, 1, Th17↓, 1, TLR4↓, 2, TNF-α↓, 4,

Synaptic & Neurotransmission ⓘ

AChE↓, 1, ADAM10↑, 1, BDNF↑, 7, PSD95↑, 1, p‑tau↓, 2, TrkB↑, 1,

Protein Aggregation ⓘ

AGEs↓, 1, Aβ↓, 7, BACE↓, 2, IDE↑, 1, PP2A↑, 1,

Drug Metabolism & Resistance ⓘ

BioAv↓, 1, BioAv↑, 4, BioAv↝, 5, Dose↝, 1, eff↓, 1, eff↑, 4, Half-Life↝, 1,

Clinical Biomarkers ⓘ

BP↓, 1, BP↝, 1, IL6?, 1, IL6↓, 2,

Functional Outcomes ⓘ

cardioP↑, 3, cognitive↑, 8, hepatoP↑, 1, memory↑, 6, motorD↑, 2, neuroP↑, 11, radioP↑, 1, RenoP↑, 1,
Total Targets: 141

Scientific Paper Hit Count for: ERK, ERK signaling

7 Magnetic Fields
6 Curcumin
5 Berberine
5 Sulforaphane (mainly Broccoli)
3 Alpha-Lipoic-Acid
3 Baicalein
3 Quercetin
3 Shikonin
3 Thymoquinone
2 Allicin (mainly Garlic)
2 Radiotherapy/Radiation
2 Propolis -bee glue
2 Chrysin
2 EGCG (Epigallocatechin Gallate)
2 Ferulic acid
2 Fisetin
2 Honokiol
2 Pterostilbene
2 Vitamin K2
1 Silver-NanoParticles
1 Apigenin (mainly Parsley)
1 Artemisinin
1 Ashwagandha(Withaferin A)
1 Baicalin
1 Bacopa monnieri
1 brusatol
1 Caffeic acid
1 Chlorogenic acid
1 Bicalutamide
1 flavonoids
1 Gambogic Acid
1 Ginseng
1 Hydrogen Gas
1 Huperzine A/Huperzia serrata
1 Luteolin
1 Lycopene
1 Magnetic Field Rotating
1 Phenylbutyrate
1 Piperine
1 Piperlongumine
1 Plumbagin
1 Cisplatin
1 Salvia officinalis
1 Rosmarinic acid
1 Aromatherapy
1 Salvia miltiorrhiza
1 Aflavin-3,3′-digallate
1 Vitamin C (Ascorbic Acid)
1 Zinc

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

ERK 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 ⓘ

Immune & Inflammatory Signaling ⓘ

Hormonal & Nuclear Receptors ⓘ

Drug Metabolism & Resistance ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

Metal & Cofactor Biology ⓘ

Mitochondria & Bioenergetics ⓘ

Core Metabolism/Glycolysis ⓘ

Cell Death ⓘ

Transcription & Epigenetics ⓘ

Protein Folding & ER Stress ⓘ

DNA Damage & Repair ⓘ

Proliferation, Differentiation & Cell State ⓘ

Migration ⓘ

Angiogenesis & Vasculature ⓘ

Barriers & Transport ⓘ

Immune & Inflammatory Signaling ⓘ

Synaptic & Neurotransmission ⓘ

Protein Aggregation ⓘ

Drug Metabolism & Resistance ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

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