ATF4 Cancer Research Results

ATF4, Activating Transcription Factor 4: Click to Expand ⟱

Source:

Type: protein

ATF4 (Activating Transcription Factor 4) is a protein that plays a crucial role in various cellular processes, including stress response, cell growth, and differentiation.
ATF4 is overexpressed in several types of cancer, including breast, lung, colon, and pancreatic cancer. The overexpression of ATF4 can contribute to cancer cell growth, survival, and resistance to chemotherapy.
ATF4 promotes cancer cell growth by regulating the expression of genes involved in cell proliferation, angiogenesis, and metastasis. It also inhibits apoptosis (programmed cell death) by regulating the expression of anti-apoptotic genes.

Scientific Papers found: Click to Expand⟱

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/DDIT3↓,
*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.

6819-

EMD,

Recent advances in the therapeutic potential of emodin for human health

Review,

Nor,

AntiCan↑, It has therapeutic effects in cancer, diabetes, neurodegenerative diseases or chronic inflammatory diseases.
*AntiDiabetic↑, anticancer, neuroprotective, antidiabetic, antioxidant and anti-inflammatory.
*neuroP↑,
*Inflam↓,
*antiOx↑,
*BioAv↓, Because its bioavailability is low, there are limitations in clinical therapeutic use.
*BioAv↑, combined administration of emodin and piperine has been observed to clinically improve emodin pharmacokinetics, increasing 221 % of the area under the curve (AUC), 258 % the maximum concentration (Cmax), and decreasing 230 % the clearance related to
*SOD↑, fig 2 antioxidant
*GPx↑,
*GSH↑,
*NRF2↑,
*ROS↓,
*lipid-P↓,
*Cyt‑c↓,
*BAX↓, fig 2 antiinflammatory
*Bcl-2↓,
*iNOS↓,
*NO↓,
*IL6↓,
*IL10↓,
*IL17↓,
*IFN-γ↓,
*NF-kB↓,
*LC3II↓,
*Akt↓,
*Beclin-1↓,
*AMPK↓, fig 2 neuroprotective
*TNF-α↓,
*PGE2↓,
*Apoptosis↓,
*Casp3↓,
*Casp9↓,
*P53↓,
*P21↓,
*NAD↓, neuronal oxidative stress
*ATP↓,
*CHOP/DDIT3↓,
*GADD34↓,
*ATF4↓,
tumCV↓, fig 2 anticancer
Apoptosis↑,
TumCG↓,
TumCI↓,
TumMeta↓,
CSCs↓, glioma stem cells ↓b-catenin, ↓Notch-1, ↓STAT3
NOTCH1↓,
STAT3↓,
eff↑, emodin combined with curcumin ↓proliferation, ↑miR-34a
miR-34a↓,
*neuroP↑, Neuroprotective LPS-stimulated mouse ↓Nrf-2, NQO1, ↓TNF-α,↓↓ IL-6, ↓NO, ↓PGE2
*BDNF↓, model of chronic stress mice in vivo ↓progression of behavioral impairments in mice ↓consumption of sucrose, ↓plasmatic corticosterone, ↓mRNA, ↓BDNF,
*hepatoP↑, Hepatoprotective rats in vivo ↓ethanol-mediated liver steatosis ↓ ALT, ↓AST, ↓ TGL
*ALAT↓,
*AST↓,
TG/TAG↓,
ROS↑, However, at higher concentrations, emodin significantly increased ROS generation and reduced cell viability.
Slug↓, expression levels of Slug (a transcription factor) were also suppressed with emodin treatment.
EMT↓, results suggested that emodin suppressed the epithelial-mesenchymal transition of cancer cells through the ILK/GSK-3β/Slug signaling pathway
Glycolysis↓, In addition, emodin inhibited glycolysis via ROS-induced inactivation of the PI3K/AKT signaling pathway.
ChemoSen↑, The study by Peng et al. [130] also showed chemosensitizing effects of emodin to cisplatin in A549 (2–20 µM, for 48 h) and H460 (0.5–10 µM) non-small cell lung cancer cells.
P-gp/ABCB1↓, The sensitization mechanism was mediated by the inhibition of P-glycoprotein (Pgp), a drug-resistant protein related to the efflux pump mechanism.
Ki-67↓, The significant reduction of Ki-67 and proliferating cell nuclear antigen (PCNA) protein levels supported the antiproliferative effect of emodin in animal models.
PCNA↓,
ER Stress↑, findings suggested that emodin exerts its apoptotic effects in a process mediated by ER stress and the activation of the TRIB3/NF-κB pathway in lung cancer cells.
TRIB3↑,
NF-kB↑,
TumMeta↑, Emodin (40 mg/kg for 7 days) significantly decreased the metastatic recurrence of breast cancer after surgery in the lungs by reducing the formation of epithelial-mesenchymal transition (EMT) and cancer stem cell (CSC).
*Imm↓, emodin may be developed as an immunosuppressive agent in case of immune activation, autoimmune disorders even in organ transplantation
*toxicity↝, An excess of emodin due to its laxative effects causes intestinal pain and severe diarrhea with subsequent electrolyte imbalance and dehydration [157]. Therefore, treatment should begin when symptoms appear, with special attention to electrolyte leve

3716-

FA,

Ferulic Acid as a Protective Antioxidant of Human Intestinal Epithelial Cells

in-vitro,

IBD,

0–500 μM for 24 h

in-vivo,

NA,

*antiOx↑, Ferulic acid (FA) is a polyphenol that is abundant in plants and has antioxidant and anti-inflammatory properties
*Inflam↓,
*ER Stress↓, FA suppressed ER stress, nitric oxide (NO) generation, and inflammation in polarized Caco-2 and T84 cells,
*other↑, FA has a protective effect on intestinal tight junctions
*angioG↑, A has been reported to induce hypoxia and enhance the angiogenesis of human umbilical vein endothelial cells (HUVEC) by increasing the expressions of HIF-1α and vascular endothelial growth factor (VEGF)
*Hif1a↑,
*VEGF↑,
*NO↓, suggesting FA attenuates NO production induced by inflammation.
*SIRT1↑, Another study suggested that FA activated SIRT1 to protect the heart from the adverse effects of ER stress via reduction of PERK/eIF2α/ATF4/CHOP pathway
*PERK↓,
*ATF4↓,
*CHOP/DDIT3↓,
*GutMicro↑, FA can mitigate intestinal inflammation, promote the growth of Bacteroides, and induce the production of SCFAs by modulating the gut microbiota in mouse and diabetic syndrome rat model

2845-

FIS,

Fisetin: A bioactive phytochemical with potential for cancer prevention and pharmacotherapy

Review,

Var,

PI3K↓, block multiple signaling pathways such as the phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) and p38
Akt↓,
mTOR↓,
p38↓,
*antiOx↑, antioxidant, anti-inflammatory, antiangiogenic, hypolipidemic, neuroprotective, and antitumor effect
*neuroP↑,
Casp3↑, U266 cancer cell line through activation of caspase-3, downregulation of Bcl-2 and Mcl-1L, upregulation of Bax, Bim and Bad
Bcl-2↓,
Mcl-1↓,
BAX↑,
BIM↑,
BAD↑,
AMPK↑, activation of 5'adenosine monophosphate-activated protein kinase (AMPK), acetyl-CoA carboxylase (ACC) and decreased phosphorylation of AKT and mTOR were also observed
ACC↑,
DNAdam↑, DNA fragmentation, mitochondrial membrane depolarizatio
MMP↓,
eff↑, fisetin in combination with a citrus flavanone, hesperetin mediated apoptosis by mitochondrial membrane depolarization and caspase-3 act
ROS↑, NCI-H460 human non-small cell lung cancer line, fisetin generated reactive oxygen species (ROS), endoplasmic reticulum (ER) stress
cl‑PARP↑, fisetin treatment resulted in PARP cleavage
Cyt‑c↑, release of cyt. c
Diablo↑, release of cyt. c and Smac/DIABLO from mitochondria,
P53↑, increased p53 protein levels
p65↓, reduced phospho-p65 and Myc oncogene expression
Myc↓,
HSP70/HSPA5↓, fisetin causes inhibition of proliferation by the modulation of heat shock protein 70 (HSP70), HSP27
HSP27↓,
COX2/PTGS2↓, anti-proliferative effects of fisetin through the activation of apoptosis via inhibition of cyclooxygenase-2 (COX-2) and Wnt/EGFR/NF-κB signaling pathways
Wnt↓,
EGFR↓,
NF-kB↓,
TumCCA↑, The anti-proliferative effects of fisetin and hesperetin were shown to be occurred through S, G2/M, and G0/G1 phase arrest in K562 cell progression
CDK2↓, decrease in levels of cyclin D1, cyclin A, Cdk-4 and Cdk-2
CDK4↓,
cycD1/CCND1↓,
cycA1/CCNA1↓,
P21↑, increase in p21 CIP1/WAF1 levels in HT-29 human colon cancer cell
MMP2↓, fisetin has exhibited tumor inhibitory effects by blocking matrix metalloproteinase-2 (MMP- 2) and MMP-9 at mRNA and protein levels,
MMP9↓,
TumMeta↓, Antimetastasis
MMP1↓, fisetin also inhibited the MMP-14, MMP-1, MMP-3, MMP-7, and MMP-9
MMP3↓,
MMP7↓,
MET↓, promotion of mesenchymal to epithelial transition associated with a decrease in mesenchymal markers i.e. N-cadherin, vimentin, snail and fibronectin and an increase in epithelial markers i.e. E-cadherin
N-cadherin↓,
Vim↓,
Snail↓,
Fibronectin↓,
E-cadherin↑,
uPA↓, fisetin suppressed the expression and activity of urokinase plasminogen activator (uPA)
ChemoSen↑, combination treatment of fisetin and sorafenib reduced the migration and invasion of BRAF-mutated melanoma cells both in in-vitro
EMT↓, inhibited epithelial to mesenchymal transition (EMT) as observed by a decrease in N-cadherin, vimentin and fibronectin and an increase in E-cadherin
Twist↓, inhibited expression of Snail1, Twist1, Slug, ZEB1 and MMP-2 and MMP-9
Zeb1↓,
cFos↓, significant decrease in NF-κB, c-Fos, and c-Jun levels
cJun↓,
EGF↓, Fisetin inhibited epidermal growth factor (EGF)
angioG↓, Antiangiogenesis
VEGF↓, decreased expression of endothelial nitric oxide synthase (eNOS) and VEGF, EGFR, COX-2
eNOS↓,
*NRF2↑, significantly increased nuclear translocation of Nrf2 and antioxidant response element (ARE) luciferase activity, leading to upregulation of HO-1 expression
HO-1↑,
NRF2↓, Fisetin also triggered the suppression of Nrf2
GSTs↓, declined placental type glutathione S-transferase (GST-p) level in the liver of the fisetin- treated rats with hepatocellular carcinoma (HCC)
ATF4↓, Fisetin also rapidly increased the levels of both Nrf2 and ATF4

7482-

H2,

Molecular Hydrogen Therapy: Mechanisms, Delivery Methods, Preventive, and Therapeutic Application

Review,

Var,

Review,

IBD,

Review,

Stroke,

Review,

Sepsis,

Review,

AD,

Dose↝, H2 can be administered exogenously and is also produced endogenously within the intestinal tract.
*Inflam↓, Anti‐Inflammatory Effect
*IL1β↓, diabetes combined with stroke, H₂ intervention downregulates the expression levels of proinflammatory factors (IL‐1β, IL‐6, TNF‐α), while activating the TLR4/NF‐κB signaling pathway to achieve neuroprotective effects
*IL6↓,
*TNF-α↓,
*neuroP↑,
*mTOR↓, sepsis model, H₂ regulates macrophage polarization (inhibiting the M1 phenotype/promoting the M2 phenotype) and inhibits (mTOR) phosphorylation, reducing the release of inflammatory mediators such as IL‐6, TNF‐α, and HMG
*IL10↑, while increasing the levels of anti‐inflammatory factors IL‐10 and Transforming Growth Factor‐beta (TGF‐β)
*TGF-β↑,
*Sepsis↓,
*NRF2↑, whereas Nrf2 induction suppresses these pathways via redox homeostasis modulation
*antiOx↑, figure 1
*Catalase↑,
*SOD↑,
*GPx↑,
*ROS↓, H₂ mediates ROS regulation through Nrf2, inhibiting NF‐κB/NLRP3 inflammasome activation and achieving an antioxidant–anti‐inflammatory synergistic effect
*HO-1↑, H2 can increase the expression of heme oxygenase‐1 (HO‐1) or activate the phosphatidylinositol‐3‐kinase (PI3K)–Akt signaling pathway to improve liver I/R injury
*PI3K↑,
*Akt↑,
*hepatoP↑,
*MPO↓, reduce myeloperoxidase (MPO) activity and IL‐1β/TNF‐α levels to alleviate myocardial injury
*cardioP↑,
CDK4↓, Studies have demonstrated that H2 inhibits CDK4 and CDK6 to restrict lung cancer progression
CDK6↑,
CD47↓, H₂ can reverse immune escape in lung cancer cells by inhibiting the expression of CD47 and activating the apoptosis program
PI3K↓, H2 promotes apoptosis by downregulating Akt phosphorylation and inhibiting the PI3K signaling pathway in non‐small cell lung cancer.
Akt↓,
Hif1a↓, inhalation of H2 suppresses Hypoxia‐Inducible Factor 1 Alpha Subunit (HIF‐1α)/NF‐κB signaling pathway activation and promotes apoptosis in HeLa cells
selectivity↑, This bidirectional regulatory capability allows H₂ to protect normal tissues from excessive apoptosis (such as inflammation‐induced cell death) while selectively inducing apoptosis in tumor cells.
*MMP↑, howed that after treating septic rats with HRS, the decline in mitochondrial membrane potential (MMP) and ATP content was improved.
*ATP↑,
*ER Stress↓, H₂ alleviated inflammation and organ damage by inhibiting ER stress and activating the autophagy pathway in septic mice
*CHOP/DDIT3↓, H2 could downregulate the expression of CHOP, caspase‐12, and GRP78, while inhibiting p38 and c‐Jun N‐terminal kinase (JNK) phosphorylation, and upregulating the LC3‐II/I ratio
*Casp12↓,
*GRP78/BiP↓,
*p38↓,
*p‑JNK↓,
*LC3‑Ⅱ/LC3‑Ⅰ↑,
*p‑eIF2α↓, HRW prevents IBD in mice by reducing levels of p‐eIF2α, ATF4, XBP1, and CHOP, key proteins in ER stress.
*ATF4↓,
*XBP-1↓,
*Imm↑, H₂ exhibit multidimensional characteristics, primarily enhancing immunity by protecting immune organs,
*IFN-γ↓, H2 treatment inhibited several T‐cell effector molecules, such as IFN‐γ, IL‐4, and GZMB
*IL4↓,
*GranB/GZMB↓,
NK cell↑, After inhaling H₂ for 2 weeks, patients with advanced non‐small cell lung cancer showed significant improvement in T‐cell exhaustion. (NK) subgroups was higher than the pretreatment percentag
radioP↑, HRS can protect against radiation‐induced immune dysfunction by restoring the number of CD4+ T and CD8+ T cells in the spleen.
*CD4+↑,
CD8+↑,
*Dose↝, Common delivery methods include inhalation, oral administration of HRW, injection of HRS, promotion of endogenous H2 production
*other↑, H2, which fall within the explosive range at concentrations ranging from 4 to 74%, it is essential to specify the concentration of H2 for inhalation therapy.
*Dose↝, China National Health Commission recommends the administration of oxygen–H2 mixture (33.3% O2 and 66.6% H2)
*antiPs↑, HRW baths exhibit inhibitory effects on inflammation and oxidative stress while demonstrating therapeutic benefits for conditions such as psoriasis
*BioAv↝, the solubility of H2 in water at room temperature and pressure is limited to a maximum of 0.8mM109, resulting in limited efficacy when orally administered.
*GutMicro↑, inhalation of H2 modulates the gut flora to ameliorate acute alcoholic liver injury. H2 altered the composition of the GM, leading to an increase in the relative abundance of Mycobacterium anisopliae and Mycobacterium thickum
Dose↝, CRC cell lines (ROK/SW480/HCT116) and xenograft mouse models,Inhalation of 66% H2 (66% H2 and 33% O2);Duration: 2 h a day for 21 days
*IBI↑, orally administered silicon H2 nanoparticles (SiH NPs) for targeted scavenging of ROS at inflammatory sites, thereby alleviating symptoms of IBD and restoring GM diversity by enhancing the abundance of beneficial bacteria.
TumCP↓, H2 inhibits tumor cell activity, proliferation, invasion, and migration through various molecular mechanisms, in a manner that depends on both dose and time.
TumCI↓,
TumCMig↓,
CD8+↑, H2 Improves Prognosis by Restoring Depleted CD8+ T Cells in Patients with CRC Cancer
PGC-1α↑, It has been shown that H2 can activate PGC‐1α to restore mitochondrial function and rescue depleted CD8+T cells
Akt↓, H2 Inhibits CRC Cell Proliferation by Suppressing the AKT/SCD1 Pathway
SCD1↓,
*MDA↓, The results showed that H2 water alone significantly improved detected antioxidant markers (SOD and CAT) and reduced MDA levels.
eff↑, combination of H2 water and 5‐fluorouracil significantly attenuated MDA levels more effectively than 5‐fluorouracil alone
*APP↓, H2 gas significantly inhibited the overexpression of APP, BACE1, and sAP, thereby reducing Aβ production.
*BACE/β-secretase↓,
*Aβ↓,
*cognitive↑, This intervention effectively halted the progression of AD, alleviating cognitive impairment, synaptic deficits, and neuronal death
*neuroP↑, regulation of GM(gutmicrobiome) by HRW considered a key mechanism underlying its neuroprotective effects.
NP/CIPN↓, mice with chemotherapy‐induced neuropathic pain caused by oxaliplatin, drinking HRW significantly reduced inflammation by inhibiting the LPS–TLR4 pathway and decreasing the expression of TNF‐α and IL‐6.
*Stroke↓, inhalation of 2% H2 gas significantly reduced levels of myocardial injury markers, such as creatine kinase‐MB and cardiac troponin‐T, while protecting myocardial tissue from further damage by inhibiting autophagy.
*NLRP3↓, daily inhalation of 2% H2 gas for 3 h over 28 days effectively suppressed the activation of the NLRP3 inflammasome, reduced cardiac fibrosis, and improved cardiac function
*ALAT↓, 4% H2 outperforming 67% H2 in reducing liver enzyme levels Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) and lipid accumulation.
*AST↓,
*LPS↓, inhalation of 4% H2 in an NAFLD rat model significantly lowered plasma LPS levels, inhibited the LPS/TLR4/NF‐κB signaling pathway to reduce liver inflammation
*hepatoP↑, drinking HRW, indicating its hepatoprotective effects
chemoP↑, injecting HRS in rats effectively reduced ALT and AST levels caused by doxorubicin, decreased ROS and MDA production, and regulated the Bax/Bcl‐2 ratio to alleviate inflammation and apoptosis.
*creat↓, mouse model of kidney injury induced by a high‐oxalate diet, HRW consumption markedly improved serum creatinine, blood urea nitrogen, and kidney injury markers such as kidney injury molecule‐1 (KIM‐1)
*Urea↓,
*RenoP↑,
*eff↑, higher concentrations of H2 gas (67%) produced more pronounced improvements in kidney histology and morphology compared with lower concentrations (4%)
Apoptosis↑, H2 gas increased apoptosis in A549 cells while reducing the expression of XIAP and BIRC3 proteins in studies on A549 cells and their nude mouse models.
XIAP↓,
IAP2/BIRC3↓,
TumVol↓, inhalation of 60% H2 gas significantly reduced tumor volume in experimental mice
MALAT1↓, In gastric cancer research, Zhu et al. [10] found that H2 gas downregulated the expression of lncRNA MALAT1 and EZH2 while upregulating miR‐124‐3p
EZH2↓,
miR-124-3p↓,
eff↑, combining platinum nanocolloid (Pt‐nc) with H2 gas effectively inhibited the growth of human promyelocytic leukemia HL60 cells
ChemoSen↑, combining H2 therapy with conventional treatments such as chemotherapy and radiotherapy, demonstrating improved efficacy and reduced side effects
*compII↑, allergic airway inflammation, showing that H2 increased ATP production as well as the activity of mitochondrial respiratory chain complexes I and III
*compIII↑,
*LDL↓, H2‐enriched water in humans, showing that supplementation with H2‐enriched water appeared to reduce serum low‐density lipoprotein cholesterol (LDL‐C) and apolipoprotein B (apoB) levels,
*Obesity↓, H2 may play a beneficial role in the prevention of potential metabolic syndrome
QoL↑, 82 patients with stage III and IV cancers receiving H2 inhalation therapy. They found that H2 inhalation improved the quality of life
PFS↑, Sixteen months of follow‐up found that progression‐free survival in the control group was lower than that in the H2 inhalation group alone, and significantly lower than that in the other three combination therapy groups.

2921-

LT,

Luteolin as a potential hepatoprotective drug: Molecular mechanisms and treatment strategies

Review,

Nor,

*hepatoP↑, Due to its excellent liver protective effect, luteolin is an attractive molecule for the development of highly promising liver protective drugs.
*AMPK↑, fig2
*SIRT1↑,
*ROS↓,
STAT3↓,
TNF-α↓,
NF-kB↓,
*IL2↓,
*IFN-γ↓,
*GSH↑,
*SREBP1/SREBF1↓,
*ZO-1↑,
*TLR4↓,
BAX↑, anti cancer
Bcl-2↓,
XIAP↓,
Fas↑,
Casp8↑,
Beclin-1↑,
*TXNIP↓, luteolin inhibited TXNIP, caspase-1, interleukin-1β (IL-1β) and IL-18 to prevent the activation of NLRP3 inflammasome, thereby alleviating liver injury.
*Casp1↓,
*IL1β↓,
*IL18↓,
*NLRP3↓,
*MDA↓, inhibiting oxidative stress and regulating the level of malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione (GSH)
*SOD↑,
*NRF2↑, luteolin promoted the activation of the Nrf2/ antioxidant response element (ARE) pathway and NF-κB cell apoptosis pathway, thereby reversing the decrease in Nrf2 levels(lead induced liver injury)
*ER Stress↓, down regulate the formation of nitrotyrosine (NT) and endoplasmic reticulum (ER) stress induced by acetaminophen, and alleviate liver injury
*ALAT↓, ↓ALT, AST, MDA, iNOS, NLRP3 ↑GSH, SOD, Nrf2
*AST↓,
*iNOS↓,
*IL6↓, ↓TXNIP, NLRP3, TNF-α, IL-6 ↑HO-1, NQO1
*HO-1↑,
*NQO1↑,
*PPARα↑, ↓TNF-α, IL-6 IL-1β, Bax ↑PPARα
*ATF4↓, ↓ALT, AST, TNF-α, IL-6, MDA, ATF-4, CHOP ↑GSH, SOD
*CHOP/DDIT3↓,
*Inflam↓, Luteolin ameliorates MAFLD through anti-inflammatory and antioxidant effects
*antiOx↑,
*GutMicro↑, luteolin could significantly enrich more than 10% of intestinal bacterial species, thereby increasing the abundance of ZO-1, down regulating intestinal permeability and plasma lipopolysaccharide

3024-

RosA,

rmMANF prevents sepsis-associated lung injury via inhibiting endoplasmic reticulum stress-induced ferroptosis in mice

in-vivo,

Sepsis,

*Ferroptosis↓, rmMANF pretreatment inhibits ferroptosis by suppressing GRP78/PERK/ATF4 axis.
*GRP78/BiP↓,
*PERK↓,
*ATF4↓,
*Sepsis↓,
*GSH↑, LPS administration mice exhibited elevated MDA immunoactivity, total iron level, and declined GSH level, and SOD, CAT activities, while these effects of LPS were effectively against by rmMANF pretreatment
*SOD↑,
*Catalase↑,

2191-

SK,

Shikonin Suppresses Skin Carcinogenesis via Inhibiting Cell Proliferation

in-vitro,

Melanoma,

PKM2↓, shikonin alone suppressed PKM2 activity
ATF4↓, Shikonin decreased the nuclear levels of ATF2 and knockdown of ATF2 suppressed the expression levels of Cdk4 and Fra-1
CDK4↓,
COX2/PTGS2↓, shikonin has been shown to inhibit TPA-induced cyclooxygenase-2 (COX-2) activation, which is mediated by suppression of MAPK signaling
MAPK↓,

Showing Research Papers: 1 to 8 of 8

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 8

Pathway results for Effect on Cancer / Diseased Cells:

Infection & Microbiome(tgid=24) ⓘ

CD8+↑, 2,
Total Targets: 114

Pathway results for Effect on Normal Cells:

NA, unassigned(tgid=0) ⓘ

compII↑, 1, Stroke↓, 1,

Redox & Oxidative Stress(tgid=1) ⓘ

antiOx↑, 5, Catalase↑, 2, Ferroptosis↓, 1, GPx↑, 2, GSH↑, 3, HO-1↑, 2, lipid-P↓, 1, MDA↓, 2, MPO↓, 1, NQO1↑, 1, NRF2↑, 4, ROS↓, 4, SOD↑, 4,

Mitochondria & Bioenergetics(tgid=3) ⓘ

ATP↓, 1, ATP↑, 1, compIII↑, 1, MMP↑, 1,

Core Metabolism/Glycolysis(tgid=4) ⓘ

ALAT↓, 3, AMPK↓, 1, AMPK↑, 1, LDL↓, 1, NAD↓, 1, PPARα↑, 1, SIRT1↑, 2, SREBP1/SREBF1↓, 1,

Cell Death(tgid=5) ⓘ

Akt↓, 1, Akt↑, 1, Apoptosis↓, 1, BAX↓, 1, Bcl-2↓, 1, Casp1↓, 1, Casp12↓, 1, Casp3↓, 1, Casp9↓, 1, Cyt‑c↓, 1, Ferroptosis↓, 1, GADD34↓, 1, GranB/GZMB↓, 1, iNOS↓, 2, p‑JNK↓, 1, p38↓, 1,

Transcription & Epigenetics(tgid=7) ⓘ

other↑, 2,

Protein Folding & ER Stress(tgid=8) ⓘ

CHOP/DDIT3↓, 4, p‑eIF2α↓, 2, ER Stress↓, 4, GRP78/BiP↓, 2, PERK↓, 2, p‑PERK↓, 1, UPR↓, 1, XBP-1↓, 1,

Autophagy & Lysosomes(tgid=9) ⓘ

Beclin-1↓, 1, LC3‑Ⅱ/LC3‑Ⅰ↑, 1, LC3II↓, 1,

DNA Damage & Repair(tgid=10) ⓘ

P53↓, 1,

Cell Cycle & Senescence(tgid=11) ⓘ

P21↓, 1,

Proliferation, Differentiation & Cell State(tgid=12) ⓘ

mTOR↓, 1, PI3K↑, 1, STAT3↑, 1,

Migration(tgid=13) ⓘ

APP↓, 1, TGF-β↑, 1, TXNIP↓, 1, ZO-1↑, 1,

Angiogenesis & Vasculature(tgid=14) ⓘ

angioG↑, 1, ATF4↓, 6, Hif1a↑, 1, NO↓, 2, VEGF↑, 1,

Barriers & Transport(tgid=15) ⓘ

IBI↑, 1,

Immune & Inflammatory Signaling(tgid=16) ⓘ

CD4+↑, 1, IFN-γ↓, 3, IL10↓, 1, IL10↑, 1, IL17↓, 1, IL18↓, 1, IL1β↓, 2, IL2↓, 1, IL4↓, 1, IL6↓, 3, Imm↓, 1, Imm↑, 1, Inflam↓, 4, JAK2↑, 1, LPS↓, 1, NF-kB↓, 1, PGE2↓, 1, TLR4↓, 1, TNF-α↓, 2,

Synaptic & Neurotransmission(tgid=18) ⓘ

BDNF↓, 1,

Protein Aggregation(tgid=19) ⓘ

Aβ↓, 1, BACE/β-secretase↓, 1, NLRP3↓, 2,

Drug Metabolism & Resistance(tgid=21) ⓘ

BioAv↓, 1, BioAv↑, 1, BioAv↝, 1, Dose↝, 2, eff↑, 1,

Clinical Biomarkers(tgid=22) ⓘ

ALAT↓, 3, AST↓, 3, creat↓, 1, GutMicro↑, 3, IL6↓, 3, Urea↓, 1,

Functional Outcomes(tgid=23) ⓘ

AntiDiabetic↑, 1, antiPs↑, 1, cardioP↑, 2, cognitive↑, 1, hepatoP↑, 4, neuroP↑, 5, Obesity↓, 1, RenoP↑, 1, toxicity↝, 1,

Infection & Microbiome(tgid=24) ⓘ

Sepsis↓, 2,
Total Targets: 114

Scientific Paper Hit Count for: ATF4, Activating Transcription Factor 4

1 Berberine
1 Emodin
1 Ferulic acid
1 Fisetin
1 Hydrogen Gas
1 Luteolin
1 Rosmarinic acid
1 Shikonin

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

ATF4 Cancer Research Results

Pathway results for Effect on Cancer / Diseased Cells:

NA, unassigned(tgid=0) ⓘ

Redox & Oxidative Stress(tgid=1) ⓘ

Mitochondria & Bioenergetics(tgid=3) ⓘ

Core Metabolism/Glycolysis(tgid=4) ⓘ

Cell Death(tgid=5) ⓘ

Transcription & Epigenetics(tgid=7) ⓘ

Protein Folding & ER Stress(tgid=8) ⓘ

Autophagy & Lysosomes(tgid=9) ⓘ

DNA Damage & Repair(tgid=10) ⓘ

Cell Cycle & Senescence(tgid=11) ⓘ

Proliferation, Differentiation & Cell State(tgid=12) ⓘ

Migration(tgid=13) ⓘ

Angiogenesis & Vasculature(tgid=14) ⓘ

Barriers & Transport(tgid=15) ⓘ

Immune & Inflammatory Signaling(tgid=16) ⓘ

Hormonal & Nuclear Receptors(tgid=20) ⓘ

Drug Metabolism & Resistance(tgid=21) ⓘ

Clinical Biomarkers(tgid=22) ⓘ

Functional Outcomes(tgid=23) ⓘ

Infection & Microbiome(tgid=24) ⓘ

Pathway results for Effect on Normal Cells:

NA, unassigned(tgid=0) ⓘ

Redox & Oxidative Stress(tgid=1) ⓘ

Mitochondria & Bioenergetics(tgid=3) ⓘ

Core Metabolism/Glycolysis(tgid=4) ⓘ

Cell Death(tgid=5) ⓘ

Transcription & Epigenetics(tgid=7) ⓘ

Protein Folding & ER Stress(tgid=8) ⓘ

Autophagy & Lysosomes(tgid=9) ⓘ

DNA Damage & Repair(tgid=10) ⓘ

Cell Cycle & Senescence(tgid=11) ⓘ

Proliferation, Differentiation & Cell State(tgid=12) ⓘ

Migration(tgid=13) ⓘ

Angiogenesis & Vasculature(tgid=14) ⓘ

Barriers & Transport(tgid=15) ⓘ

Immune & Inflammatory Signaling(tgid=16) ⓘ

Synaptic & Neurotransmission(tgid=18) ⓘ

Protein Aggregation(tgid=19) ⓘ

Drug Metabolism & Resistance(tgid=21) ⓘ

Clinical Biomarkers(tgid=22) ⓘ

Functional Outcomes(tgid=23) ⓘ

Infection & Microbiome(tgid=24) ⓘ

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