eIF2α Cancer Research Results

eIF2α, Eukaryotic translation initiation factor 2: Click to Expand ⟱

Source:

Type:

The phosphorylation of eIF2α is carried out by a family of four kinases, PERK (PKR-like ER kinase), PKR (protein kinase double-stranded RNA-dependent), GCN2 (general control non-derepressible-2), and HRI (heme-regulated inhibitor).
Eukaryotic translation initiation factor 2 alpha (eIF2α) is a critical protein involved in the initiation of protein synthesis in eukaryotic cells. It plays a key role in regulating translation in response to various cellular stresses, including nutrient deprivation, oxidative stress, and viral infection. The phosphorylation status of eIF2α is particularly important, as it can influence cell survival, apoptosis, and the overall stress response.

The phosphorylation status of eIF2α can have significant prognostic implications in cancer. Elevated levels of phosphorylated eIF2α are often associated with poor prognosis in several cancer types, as they may indicate a tumor's ability to adapt to stress and survive in unfavorable conditions.

Scientific Papers found: Click to Expand⟱

3156-

Ash,

Withaferin A: From ayurvedic folk medicine to preclinical anti-cancer drug

Review,

Var,

MAPK↑, Figure 3
p38↑,
BAX↑,
BIM↑,
CHOP↑,
ROS↑,
DR5↑,
Apoptosis↑,
Ferroptosis↑,
GPx4↓,
BioAv↝, WA has a rapid oral absorption and reaches to peak plasma concentration of around 16.69 Â± 4.02 ng/ml within 10 min after oral administration of Withania somnifera aqueous extract at dose of 1000 mg/kg, which is equivalent to 0.458 mg/kg of WA
HSP90↓, table 1 10uM) were found to inhibit the chaperone activity of HSP90
RET↓,
E6↓,
E7↓,
Akt↓,
cMET↓,
Glycolysis↓, by suppressing the glycolysis and tricarboxylic (TCA) cycle
TCA↓,
NOTCH1↓,
STAT3↓,
AP-1↓,
PI3K↓,
eIF2α↓,
HO-1↑,
TumCCA↑, WA (1--3 uM) have been reported to inhibit cell proliferation by inducing G2 and M phase cycle arrest inovarian, breast, prostate, gastric and myelodysplastic/leukemic cancer cells and osteosarcoma
CDK1↓, WA is able to decrease the cyclin-dependent kinase 1 (Cdk1) activity and prevent Cdk1/cyclin B1 complex formation, which are key steps in cell cycle progression
*hepatoP↑, A treatment (40 mg/kg) reduces acetaminophen-induced liver injury (AILI) in mouse models and decreases H 2O 2-induced glutathione (GSH) depletion and necrosis in hepatocyte
*GSH↑,
*NRF2↑, WA triggers an anti-oxidant response after acetaminophen overdose by enhancing hepatic transcription of the nuclear factor erythroid 2ârelated factor 2 (NRF2)-responsive gene
Wnt↓, indirectly inhibit Wnt
EMT↓, WA can also block tumor metastasis through reduced expression of epithelial mesenchymal transition (EMT) markers.
uPA↓, WA (700 nM) exert anti-meta-static activities in breast cancer cells through inhibition of the urokinase-type plasminogen activator (uPA) protease
CSCs↓, s WA (125-500 nM) suppress tumor sphere formation indicating that the self-renewal of CSC is abolished
Nanog↓, loss of these CSC-specific characteristics is reflected in the loss of typical stem cell markers such as ALDH1A, Nanog, Sox2, CD44 and CD24
SOX2↓,
CD44↓,
lactateProd↓, drop in lactate levels compared to control mice.
Iron↑, Furthermore, we found that WA elevates the levels of intracellular labile ferrous iron (Fe +2 ) through excessive activation of heme oxygenase-1 (HMOX1), which independently causes accumulation of toxic lipid radicals and ensuing ferroptosis
NF-kB↓, nhibition of NF-kB kinase signaling pathway

2676-

BBR,

Berberine protects rat heart from ischemia/reperfusion injury via activating JAK2/STAT3 signaling and attenuating endoplasmic reticulum stress

in-vivo,

Nor,

Male rats were treated with BBR (200 mg·kg−1·d−1, ig) for 2 weeks, and then subjected to MI/R surgery.

in-vivo,

CardioV,

*cardioP↑, Pretreatment with BBR significantly reduced MI/R-induced myocardial infarct size, improved cardiac function, and suppressed myocardial apoptosis and oxidative damage.
*ROS↓,
*ER Stress↓, pretreatment with BBR suppressed MI/R-induced ER stress
*p‑PERK↓, evidenced by down-regulating the phosphorylation levels of myocardial PERK and eIF2α and the expression of ATF4 and CHOP in heart tissues.
*p‑eIF2α↓,
*ATF4↓,
CHOP↓,
*JAK2↑, Pretreatment with BBR also activated the JAK2/STAT3 signaling pathway in heart tissues
*STAT3↑,
*UPR↓, Therefore, reducing excessive UPR, also referred to as ER stress, is of great importance in ameliorating MI/R injury.

2679-

BBR,

Berberine Improves Behavioral and Cognitive Deficits in a Mouse Model of Alzheimer’s Disease via Regulation of β-Amyloid Production and Endoplasmic Reticulum Stress

in-vivo,

AD,

*cognitive↑, berberine could improve cognitive deficits in the triple-transgenic mouse model of Alzheimer’s disease (3 × Tg AD) mice.
PERK↓, berberine treatment may inhibit PERK/eIF2α signaling-mediated BACE1 translation, thus reducing Aβ production and resultant neuronal apoptosis
*eIF2α↓,
*neuroP↑, berberine may have neuroprotective effects, via attenuation of ER stress and oxidative stress.
*ER Stress↓,
*ROS↓,

2683-

BBR,

Berberine reduces endoplasmic reticulum stress and improves insulin signal transduction in Hep G2 cells

in-vitro,

Liver,

HepG2

JNK↓, while the activation of JNK was blocked
p‑PERK↓, phosphorylation both on PERK and eIF2α were inhibited in cells pretreated with berberine.
p‑eIF2α↓,
*ER Stress↓, antidiabetic effect of berberine in Hep G2 cells maybe related to attenuation of ER stress

5880-

CAR,

In vitro and in vivo antitumor potential of carvacrol nanoemulsion against human lung adenocarcinoma A549 cells via mitochondrial mediated apoptosis

vitro+vivo,

Lung,

A549

nude mice, present study commenced to formulate CANE by an energy intensive ultrasonication method.

in-vitro,

Nor,

BEAS-2B

in-vitro,

Lung,

PC9

Dose↝, prepare a carvacrol nanoemulsion (CANE) using an ultrasonication technique and further evaluation of its anticancer potential against human lung adenocarcinoma A549 cells. (160nm)
mt-ROS↑, The CANE induced reactive oxygen species (ROS) production in A549 cells,
p‑JNK↑, leading to activation of key regulators of apoptosis such as p-JNK, Bax and Bcl2 as well as release of cytochrome C, and activation of the caspase cascade.
BAX↑,
Cyt‑c↑,
Casp↑,
AntiTum↑, CANE displayed a strong antitumor potential in vivo using an athymic nude mice model.
ER Stress↑, Abnormally high ROS levels create ER stress with the involvement of three major signaling proteins IRE1-α, PERK and ATF-6
LDH↑, higher LDH activity, which is a well-established biomarker released by damaged cells, was observed in CANE-treated cells
selectivity↑, CANE displayed no cytotoxicity up to 100 µg/ml against normal bronchial epithelium cells (BEAS-2B)
Apoptosis↑, Induction of apoptosis and ROS production in the presence of CANE
DNAdam↑, potential role on DNA damage and chromatin condensation
IRE1↑, We observed a higher expression of IRE1-α in CANE treated cells
XBP-1↑, similar expression pattern for XBP-1
CHOP↓, down-regulation of CHOP, p-eIF2α, and GRP78 was observed in CANE-treated cells
p‑eIF2α↓,
GRP78/BiP↓,
Ca+2↑, increase of Ca+2 levels in CANE-treated cells. A 2.5 fold higher Ca+2 was observed at 100 μg/ml CANE treated cells
MMP↓, CANE severely altered mitochondrial membrane potential (Δψm) in a dose-dependent manner.
Bcl-2↓, up- and down-regulation of pro-apoptotic (Bax) and anti-apoptotic (Bcl2) proteins
Casp3↑, higher levels of cleaved caspase-9 and caspase-3 in cells treated with CANE in a dose-dependent manner
Casp9↑,
eff↓, To confirm this, A549 cells were first treated with N-acetyl-L-cysteine NAC (5 mM), a strong scavenger of ROS, prior to CANE (100 µg/ml) treatment and observed a marked reduction in ROS generation
TumW↓, A significant (p < 0.05) 34.2 and 62.1% reduction in tumor weight was observed in the mice treated with 50 and 100 mg/Kg CANE, orally three times in a week
Weight↑, body weights of 100 mg/kg CANE treated mice remained static up to the second week and increased further up to 4 weeks
eff↑, ultrasonication consider as simple, cost-effective, clean and prompt aseptic technique16, wherein large droplets ruptured into small droplets by ultrasound leading to the formation of nano-scale droplets
eff↑, We selected polysorbate 80 as a surfactant (HLB, 15), which is regarded as safe for using in pharmaceutical and food industries1

3202-

EGCG,

Epigallocatechin-3-gallate enhances ER stress-induced cancer cell apoptosis by directly targeting PARP16 activity

in-vitro,

Cerv,

HeLa

100uM

in-vitro,

HCC,

QGY-7703

PARP16↓, (EGCG) as a potential inhibitor of PARP16.
p‑PERK↓, EGCG suppressed the ER stress-induced phosphorylation of PERK and the transcription of unfolded protein response-related genes,
Apoptosis↑, leading to dramatically increase of cancer cells apoptosis
eIF2α↓, EGCG suppressed the phosphorylation of PERK and eIF2α induced by ER stress.
UPR↓, UPR-related gene was dramatically induced by BFA and TUN, and this induction was suppressed by treatment of Hela cells with EGCG, further suggesting that EGCG suppressed the UPR induced by ER stress.
ER Stress↑, EGCG can dramatically inhibit the activity of PARP16, and then suppressed the ER stress-induced PERK phosphorylation, leading to dramatical increase of the ER stress-induced apoptosis of cancer cells.
eff↑, These results indicate that EGCG can be used in combination with ER stress-induced drugs to treat the cancer cell.
GRP78/BiP↓, EGCG had previously been found to bind to the ATP-binding domain of glucose regulate protein 78 (GRP78),

3337-

QC,

Endoplasmic Reticulum Stress-Relieving Effect of Quercetin in Thapsigargin-Treated Hepatocytes

in-vitro,

NA,

HepG2

*Inflam↓, quercetin exerts anti-inflammatory and anti–insulin resistance actions by suppressing UPR in cells experiencing ER stress
*UPR↓,
*GRP58↓, (GRP78) and the downstream proteins such as X-box binding protein 1 (XBP1). The increased expression was significantly inhibited by quercetin, indicating that this compound can relieve ER stress
*XBP-1↓,
*ER Stress↓, previous reports as well as our results, we suggest that quercetin can inhibit ER stress in hepatocytes
*antiOx↑, Quercetin, a well-known antioxidant, is one of the most abundant flavonols in vegetables and fruits and has been shown to have many pharmacological actions
TNF-α↓, Quercetin suppressed the increased expression of TNF-α significantly and dose-dependently
p‑eIF2α↓, quercetin treatment suppressed the phosphorylation of eIF2α, IRE1α and JNK and the mRNA expression of XBP-1, GRP78 and CHOP
p‑IRE1↓,
p‑JNK↓,
CHOP↓,

2354-

SK,

PKM2-dependent glycolysis promotes NLRP3 and AIM2 inflammasome activation

in-vivo,

Sepsis,

mice

PKM2↓, Shikonin is a potent PKM2 inhibitor in cancer cells and macrophages
*PKM2↓,
*IL1β↓, Shikonin dose-dependently inhibited IL-1β, IL-18 and HMGB1 release in activated BMDMs following treatment with NLRP3 inflammasome activator (for example, ATP) or AIM2 inflammasome activator
*IL18↓,
*HMGB1↓,
*Casp1↓, shikonin significantly inhibited caspase-1 activation triggered by stimulation with ATP
*NLRP3↓, pharmacologic inhibition of PKM2 by shikonin selectively suppresses NLRP3 and AIM2 inflammasome activation.
*AIM2↓,
*p‑eIF2α↓, Shikonin inhibited EIF2AK2 phosphorylation (Fig. 6a) and caspase-1 activity (Fig. 6b) in PMs obtained from mice subjected to lethal endotoxemia or polymicrobial sepsis.
*Sepsis↓,

965-

SK,

Shikonin suppresses proliferation and induces cell cycle arrest through the inhibition of hypoxia-inducible factor-1α signaling

in-vitro,

CRC,

HCT116

(0.3 to 30 uM)

shikonin did not adversely affect cell viability up to a concentration of 10 uM

in-vitro,

CRC,

SW-620

Hif1a↓, shikonin inhibited HIF-1α protein synthesis without affecting the expression of HIF-1α mRNA or degrading HIF-1α protein
ROS↓, shikonin resulted in a significant decrease of hypoxia-induced ROS production in HCT116 and SW620 cells
mTOR↓,
p70S6↓,
4E-BP1↓,
eIF2α↓,
TumCCA↑, HCT116 cells
TumCP↓, HCT116 and SW620
Half-Life↝, shikonin-treated cells (Fig. S1), showing the half-life was around 50 min in HCT116 and SW620 cells.

3427-

TQ,

Chemopreventive and Anticancer Effects of Thymoquinone: Cellular and Molecular Targets

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

3149-

VitC,

Hepatoprotective benefits of vitamin C against perfluorooctane sulfonate-induced liver damage in mice through suppressing inflammatory reaction and ER stress

in-vivo,

Nor,

mice

*hepatoP↑, Hepatoprotective benefits of vitamin C against perfluorooctane sulfonate-induced liver damage in mice
*ALAT↓, showed in reductions of serological levels of transaminases (ALT and AST), lipids (TG and TC), fasting glucose and insulin, inflammatory cytokines (TNF-α and IL6)
*AST↓,
*TNF-α↓,
*IL6↓,
*ER Stress↓, Further, intrahepatic expressions of endoplasmic reticulum (ER) stress-based ATF6, eIF2α, GRP78, XBP1 proteins were down-regulated by treatments of VC.
*ATF6↓,
*eIF2α↓,
*GRP78/BiP↓,
*XBP-1↓,
*Inflam↓, suppressing hepatocellular inflammatory reaction and ER stress.

Showing Research Papers: 1 to 11 of 11

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 11

Pathway results for Effect on Cancer / Diseased Cells:

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

antiOx↑, 1, GSH↑, 1, NRF2↑, 1, ROS↓, 2,

Core Metabolism/Glycolysis ⓘ

ALAT↓, 1, PKM2↓, 1,

Cell Death ⓘ

Casp1↓, 1, GRP58↓, 1,

Protein Folding & ER Stress ⓘ

ATF6↓, 1, eIF2α↓, 2, p‑eIF2α↓, 2, ER Stress↓, 5, GRP78/BiP↓, 1, p‑PERK↓, 1, UPR↓, 2, XBP-1↓, 2,

Proliferation, Differentiation & Cell State ⓘ

STAT3↑, 1,

Angiogenesis & Vasculature ⓘ

ATF4↓, 1,

Immune & Inflammatory Signaling ⓘ

AIM2↓, 1, HMGB1↓, 1, IL18↓, 1, IL1β↓, 1, IL6↓, 1, Inflam↓, 2, JAK2↑, 1, TNF-α↓, 1,

Protein Aggregation ⓘ

NLRP3↓, 1,

Clinical Biomarkers ⓘ

ALAT↓, 1, AST↓, 1, IL6↓, 1,

Functional Outcomes ⓘ

cardioP↑, 1, cognitive↑, 1, hepatoP↑, 2, neuroP↑, 1,

Infection & Microbiome ⓘ

Sepsis↓, 1,
Total Targets: 35

Scientific Paper Hit Count for: eIF2α, Eukaryotic translation initiation factor 2

3 Berberine
2 Shikonin
1 Ashwagandha(Withaferin A)
1 Carvacrol
1 EGCG (Epigallocatechin Gallate)
1 Quercetin
1 Thymoquinone
1 Vitamin C (Ascorbic Acid)

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

eIF2α Cancer Research Results

Pathway results for Effect on Cancer / Diseased Cells:

Redox & Oxidative Stress ⓘ

Mitochondria & Bioenergetics ⓘ

Core Metabolism/Glycolysis ⓘ

Cell Death ⓘ

Kinase & Signal Transduction ⓘ

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 ⓘ

Core Metabolism/Glycolysis ⓘ

Cell Death ⓘ

Protein Folding & ER Stress ⓘ

Proliferation, Differentiation & Cell State ⓘ

Angiogenesis & Vasculature ⓘ

Immune & Inflammatory Signaling ⓘ

Protein Aggregation ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

Infection & Microbiome ⓘ

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