GPx4 Cancer Research Results

GPx4, Glutathione Peroxidase 4: Click to Expand ⟱

Source:

Type:

GPX4 (Glutathione Peroxidase 4) is a selenoprotein that plays a crucial role in the regulation of ferroptosis, a form of programmed cell death characterized by the iron-dependent accumulation of lipid reactive oxygen species (ROS).
GPX4 has been found to be upregulated in several tumor types, promoting cancer cell survival and resistance to therapy. For instance, GPX4 overexpression has been observed in renal cell carcinoma, pancreatic ductal adenocarcinoma, and triple-negative breast cancer, among others. -GPX4 is known as a lipid peroxidation inhibitor protein, and its antioxidant effect is closely related to ferrous iron
-GPX4 is a confirmed key regulator of ferroptosis.(downregulation of xCT and GPX4, confirming induces ferroptosis

Scientific Papers found: Click to Expand⟱

3345-

ART/DHA,

Dihydroartemisinin-induced unfolded protein response feedback attenuates ferroptosis via PERK/ATF4/HSPA5 pathway in glioma cells

in-vitro,

GBM,

ROS↑, Dihydroartemisinin (DHA) has been shown to exert anticancer activity through iron-dependent reactive oxygen species (ROS) generation, which is similar to ferroptosis, a novel form of cell death
Ferroptosis↑, DHA induced ferroptosis in glioma cells, as characterized by iron-dependent cell death accompanied with ROS generation and lipid peroxidation.
lipid-P↑,
HSP70/HSPA5↑, DHA treatment simultaneously activated a feedback pathway of ferroptosis by increasing the expression of heat shock protein family A (Hsp70) member 5 (HSPA5)
ER Stress↑, DHA caused endoplasmic reticulum (ER) stress in glioma cells, which resulted in the induction of HSPA5 expression by protein kinase R-like ER kinase (PERK)-upregulated activating transcription factor 4 (ATF4)
ATF4↑,
GRP78/BiP↑, HSPA5
MDA↑, DHA significantly increased lipid ROS and MDA levels in glioma cells in a dose- and time-dependent manner.
GSH↓, As an important antioxidant, reduced form GSH was exhausted by DHA
eff↑, Inhibitor of HSPA5 synergistically enhanced anti-tumor effects of DHA
GPx4↑, DHA induced-ER stress in turn activated cell protection against ferroptosis through PERK-ATF4- HSPA5 activation, which promoted the expression of GPX4 to detoxify peroxidized membrane lipids

5925-

CAR,

Neuroprotective effects of carvacrol against Alzheimer’s disease and other neurodegenerative diseases: A review

Review,

AD,

Review,

Park,

Review,

Stroke,

*Inflam↓, anti-inflammatory, antioxidant, and AChEI properties
*antiOx↑,
*AChE↓,
*BBB↑, Carvacrol is able to cross the blood brain barrier easily, notably improving its therapeutic efficacy in neurodegenerative disorders
*cardioP↑, prevention of many chronic diseases, such as cancer as well as infectious, cardiovascular and neurodegenerative diseases
*neuroP↑, Extensive researches have revealed carvacrol neuroprotective properties
*memory↑, memory-enhancing activities
*TAC↑, Carvacrol has antioxidant activity and was shown to act as a dietary phyto-additive to boost animal antioxidant status (sharifi-Rad et al., 2018
*ROS↓, carvacrol could protect neuronal injuries against Aluminum-induced oxidative stress leading to lipid peroxidation
*lipid-P↓,
*MDA↓, carvacrol has been indicated to reduce malondialdehyde (MDA) and neuronal cell necrosis, and increase superoxide dismutase (SOD) and catalase (CAT) activity levels in the hippocampus (
*SOD↑,
*Catalase↑,
*NRF2↑, carvacrol activated nuclear factor-erythroid 2-related factor 2 (Nrf2) as an endogenous antioxidant
*cognitive↑, Carvacrol administration (25, 50, and 100 mg/kg) during 21 days attenuated memory impairments and enhanced cognition compared to the control group.
*IL1β↓, Carvacrol administration diminished the expression of interleukin-1β (IL-1β), cyclooxygenase-2 (COX-2), and tumor necrosis factor-α (TNF-α).
*COX2/PTGS2↓,
*TNF-α↓,
*TLR4↓, carvacrol could significantly decrease Toll-like receptor 4 (TLR4) and increase brain-derived neurotrophic factor (BDNF) expression.
*BDNF↑,
*PKCδ↑, carvacrol and thymol might have protective ability on cognitive function in AD by activation of PKC pathway
*5LO↓, Carvacrol inhibited AChE and lipoxygenase activity that supports its anti-inflammation and anti-Alzheimer effects
*TRPM7↓, Reduced caspase-3 levels, and TRPM7 channels inhibitor
*GSH↑, Antioxidant activity, Increased glutathione
*other↑, revealed a remarkable neuroprotective action of carvacrol in cerebral ischemia in animal models
*Ferroptosis↓, via ferroptosis inhibition by elevating GPx4 expression
*GPx4↑,

6983-

Form,

Formononetin enhances angiogenesis in diabetic wounds by inhibiting ferroptosis through suppression of mtROS-mediated xCT/GPX4 upregulation

vitro+vivo,

Nor,

HUVECs

mice

vitro+vivo,

Diabetic,

*BloodF↑, Formononetin (FMN), a phytoestrogen from Astragalus roots, is traditionally used to enhance blood function and microcirculation; however, its mechanism remains unclear.
*Ferroptosis↓, FMN effectively reduced ferroptosis markers in HG-treated HUVECs,
*eff↓, and Erastin treatment abolished this protective effect.
*mtDam↓, block ferroptosis through two mechanisms: restoration of mitochondrial integrity and reactivation of the xCT/GPX4 antioxidant system
*xCT/SLC7A11↑,
*GPx4↑,
*Wound Healing↑, When we tested FMN in diabetic mice, wound closure rates improved substantially, the expression of xCT and GPX4 was increased, and CD31 expression in wound vessels increased, which matched what we observed in vitro.
*CD31/PECAM-1↑,
*mt-ROS↓, mitigation of mitochondrial reactive oxygen species (mtROS) accumulation through xCT/GPX4 activation.

2082-

HNK,

Revealing the role of honokiol in human glioma cells by RNA-seq analysis

in-vitro,

GBM,

U87MG

36.27 μM

In U87-MG cells, the optimum concentration of honokiol was 20 µM, and the optimum time was 48 h

in-vitro,

GBM,

U251

59.53 μM

n U251-MG cells, the optimum concentration of honokiol was 40 µM, and the optimum time was 48 h

AntiCan↑, In summary, studies have demonstrated that honokiol has multiple anticancer effects
TumCP↑, honokiol suppresses cell proliferation, and promotes autophagy and apoptosis
TumAuto↑,
Apoptosis↑,
*BioAv↑, honokiol could improve bioavailability in nerve tissue through passing the blood-brain barrie
*neuroP↑, honokiol has neuroprotective effects.
*NF-kB↑, honokiol could reduce cytokine production and stimulate glial nuclear factor kappa B (NFκB) to eliminate the inflammatory response during cerebral ischemia-reperfusion activity
MAPK↑, honokiol activated cells MAPK signaling pathway in human glioma cells
GPx4↑, The results showed that the ferroptosis-associated protein GPX4 was suppressed in honokiol-treated cells compared to control cells.
Tf↑, Ferroptosis-associated protein TF was upregulated in both honokiol-treated cell lines compared to the control
BAX↑, BAX was increased, and the expression of Bcl-2 was suppressed in both honokiol-treated cells, indicating that honokiol induced apoptosis in the human glioma cell lines U87-MG and U251-MG.
Bcl-2↓,
antiOx↑, Researchers have found that the antioxidant capacity of honokiol is 1000 times greater than that of vitamin E
Hif1a↓, reduce HIF-1α protein levels and suppress hypoxia-related signaling pathways
Ferroptosis↑, Honokiol activated ferroptosis in human glioma cells

7562-

HYP,

doxoR,

Hyperoside Inhibits Doxorubicin-Induced Ferroptosis in Cardiomyocytes via the Nrf2/GPX4 Pathway

in-vivo,

Nor,

urine model of DOX-induced cardiotoxicity with Hyp co-treatment.

*ROS↓, Hyperoside (Hyp) exhibits notable protective effects by targeting oxidative stress, ferroptosis, and apoptosis.
*Ferroptosis↓,
*Apoptosis↓,
*cardioP↑, Hyp co-administration mitigated doxorubicin-induced cardiac impairment in mice, demonstrated by enhanced ejection fraction (EF) and fractional shortening (FS), diminished inflammatory cell infiltration and fibrotic changes
*MDA↓, Hyp reduced oxidative stress (lower MDA, higher SOD and GSH-Px activity), inhibited ferroptosis (decreased intracellular Fe2 + , MDA, 4-HNE, PTGS2, and ASCL4; increased GSH and Ferritin),
*SOD↑,
*GPx↑,
*i-Iron↓,
*4-HNE↓,
*GSH↑,
*Ferritin↑,
*ACSL4↓,
*NRF2↑, Mechanistically, Hyp activated the Nrf2/GPX4 axis: it promoted Nrf2 nuclear translocation, upregulated GPX4 expression as shown by molecular docking.
*GPx4↑,

7766-

ISL,

Isoliquiritigenin alleviates myocardial ischemia-reperfusion injury by regulating the Nrf2/HO-1/SLC7a11/GPX4 axis in mice

in-vivo,

Stroke,

mice

*ROS↓, ISL significantly attenuated H/R-triggered production of reactive oxygen species in NMCM, reduced the expression of malondialdehyde and the activity of lactate dehydrogenase, enhanced superoxide dismutase and catalase activity,
*MDA↓,
*LDH↑,
*SOD↑,
*Catalase↑,
*NRF2↑, and increased the expression of nuclear factor E2-related factor 2 (Nrf2) and its downstream heme oxygenase 1 (HO-1), thereby mitigating oxidative stress damage.
*i-Iron↓, ISL reduced intracellular free iron accumulation, up-regulated glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11) expression, and inhibited lipid peroxidation accumulation, thereby alleviating ferroptosis.
*GPx4↑,
*xCT/SLC7A11↑,
*lipid-P↓,
*Ferroptosis↓,
*HO-1↑, ISL treatment increased the levels of HO-1, GPX4, and SLC7A11, inhibited the expression of ACSL4
*ACSL4↓,
*mtDam↓, alleviated mitochondrial damage, and ferroptosis, ultimately reducing myocardial infarction area and injury induced by I/R.
*Stroke↓,

2249-

MF,

Pulsed electromagnetic fields modulate energy metabolism during wound healing process: an in vitro model study

in-vitro,

Nor,

L929

4mT, 80 Hz

 pulsed burst (burst width, 2 ms; pulse width, 10.5 ms).

*TumCMig↑, PEMFs with specific parameter (4mT, 80 Hz) promoted cell migration and viability.
*tumCV↑,
*Glycolysis↑, PEMFs-exposed L929 cells was highly glycolytic for energy generation
*ROS↓, PEMFs enhanced intracellular acidification and maintained low level of intracellular ROS in L929 cells.
*mitResp↓, shifting from mitochondrial respiration to glycolysis
*other↝, Furthermore, the analysis of ECAR/ OCR basal ratio demonstrated a tendency toward to glycolytic phenotype in L929 cells under PEMF exposure, compared to control group
*OXPHOS↓, PEMFs promoted the transformation of energy metabolism pattern from oxidative phosphorylation to aerobic glycolysis
*pH↑, result of pH detection by flow cytometer indicated the pH level in L929 cells was significantly increased in the PEMFs group compared to the control group
*antiOx↑, PEMFs upregulated the expression of antioxidant or glycolysis related genes
*PFKM↑, Pfkm, Pfkl, Pfkp, Pkm2, Hk2, Glut1, were also significantly up-regulated in the PEMFs group
*PFKL↑,
*PKM2↑,
*HK2↑,
*GLUT1↑,
*GPx1↑, GPX1, GPX4 and Sod 1 expression were significantly higher in the PEMFs group compared to the control group
*GPx4↑,
*SOD1↑,

525-

MF,

Pulsed electromagnetic fields regulate metabolic reprogramming and mitochondrial fission in endothelial cells for angiogenesis

in-vitro,

Nor,

HUVECs

4mT,  80 Hz

*angioG↑, PEMFs promoted a shift in the energy metabolism pattern of HUVECs from oxidative phosphorylation to aerobic glycolysis.
*GPx1↑, 4x
*GPx4↑, 2.2x
*SOD↑, SOD1/2 3.5x
*PFKM↑, 3x
*PFKL↑, 2.5x
*PKM2↑, 2.6x : activation of PKM2 enhanced angiogenesis in endothelial cells (ECs) by modulating glycolysis, mitochondrial fission, and fusion
*PFKP↑, 2.8x
*HK2↑, 4x
*GLUT1↑, 1.5x
*GLUT4↑, 1.6x
*ROS↓, reminder: normal HUVECs cells
*MMP↝, no damage, (normal cells)
*Glycolysis↑, (PFKL, PFKLM, PFKP, PKM2, and HK2) encoding the three key regulatory enzymes of glycolysis, hexokinase, phosphofructokinase, and pyruvate kinase, sharply increased when HUVECs were exposed to PEMFs
*OXPHOS↓, PEMFs promoted a shift in the energy metabolism pattern of HUVECs from oxidative phosphorylation to aerobic glycolysis

4102-

MF,

Modulation of antioxidant enzyme gene expression by extremely low frequency electromagnetic field in post-stroke patients

Human,

Stroke,

40 Hz frequency at 7 milliTesla, for 15 minutes per day, five days a week, over a four‑week

 Forty-eight post-stroke patients

*Catalase↑, We observed that after ELF-EMF therapy, the mRNA expression of the studied genes (CAT, SOD1, SOD2, GPx1, and GPx4) significantly increased, which enhanced the antioxidant defence of the body.
*SOD1↑,
*SOD2↑,
*GPx1↑,
*GPx4↑,
*Dose↝, 40 Hz frequency at 7 milliTesla, for 15 minutes per day, five days a week, over a four‑week

3457-

MF,

Cellular stress response to extremely low‐frequency electromagnetic fields (ELF‐EMF): An explanation for controversial effects of ELF‐EMF on apoptosis

Review,

Var,

Apoptosis↑, Ding et al., 8 it was demonstrated that 24‐h exposure to 60 Hz, 5 mT ELF‐EMF could potentiate apoptosis induced by H2O2 in HL‐60 leukaemia cell lines.
H2O2↑,
ROS↑, One of the main mechanisms proposed for defining anticancer effects of ELF‐EMF is induction of apoptosis through upregulation of reactive oxygen species (ROS) which has also been confirmed by different experimental studies.
eff↑, intermittent 100 Hz, 0.7 mT EMF significantly enhanced rate of apoptosis in human hepatoma cell lines pretreated with low‐dose X‐ray radiation.
eff↑, 50 Hz, 45 ± 5 mT pulsed EMF, significantly potentiated rate of apoptosis induced by cyclophosphamide and colchicine
Ca+2↑, Over the past few years, lots of data have shown that ELF‐EMF exposure regulates intracellular Ca2+ level
MAPK↑, Mitogen‐activated protein kinase (MAPK) cascades are among the other important signalling cascades which are stimulated upon exposure to ELF‐EMF in several types of examined cells
*Catalase↑, ELF‐EMF exposure can upregulate expression of different antioxidant target genes including CAT, SOD1, SOD2, GPx1 and GPx4.
*SOD1↑,
*GPx1↑,
*GPx4↑,
*NRF2↑, Activation and upregulation of Nrf2 expression, the master redox‐sensing transcription factor may be the most prominent example in this regard which has been confirmed in a Huntington's disease‐like rat model.
TumAuto↑, Activation of autophagy, ER stress, heat‐shock response and sirtuin 3 expression are among the other identified cellular stress responses to ELF‐EMF exposure
ER Stress↑,
HSPs↑,
SIRT3↑,
ChemoSen↑, Contrarily, when chemotherapy and ELF‐EMF exposure are performed simultaneously, this increase in ROS levels potentiates the oxidative stress induced by chemotherapeutic agents
UPR↑, In consequence of ER stress, cells begin to initiate UPR to counteract stressful condition.
other↑, Since the only proven effects of ELF‐EMF exposure on cells are cellular adaptive responses, ROS overproduction and intracellular calcium overload
PI3K↓, figure 3
JNK↑,
p38↑,
eff↓, ontrarily, when cells are exposed to ELF‐EMF, a new source of ROS production is introduced in cells which can at least partially reverse anticancer effects observed with cell's treatment with melatonin.
*toxicity?, More importantly, ELF‐EMF exposure to normal cells in most cases has shown to be safe and un‐harmful.

3567-

MFrot,

MF,

The Effect of Extremely Low-Frequency Magnetic Field on Stroke Patients: A Systematic Review

Review,

Stroke,

*eff↑, All included studies showed a beneficial effect of ELF-MFs on stroke patients
*ROS↓, Improvements were observed in domains such as oxidative stress, inflammation, ischemic lesion size, functional status, depressive symptoms and cognitive abilities.
*Inflam↓,
*cognitive↑, An improvement in cognitive abilities reported in some of the included studies [25,26,27,28] is in line with other researchers’ finding
*Catalase↑, Cichoń et al. [27] also showed that catalase activity in erythrocytes and superoxide dismutase were significantly higher in the experimental group than in the control group.
*SOD↑,
*SOD1↑, similar effect was observed in regard to SOD1 and SOD2 mRNA levels.
*SOD2↑,
*GPx1↑, ELF-MFs impacted also the expression of GPx1 and GPx4 mRNA, which increased in the experimental group about 160% (p < 0.001) and 140% (p < 0.001), respectively.
*GPx4↑,
*IL1β↑, blood samples of IL-1β in the experimental group after 10 sessions of rehabilitation which involved ELF-MFs were significantly higher than in the control group
*neuroP↑, majority of the articles included in this study, a neuroprotective effect of ELF-MFs was indicated
*toxicity∅, Particularly noteworthy is the fact that none of the studies included in this review reported any negative side effects of ELF-MFs.

3023-

RosA,

Rosmarinic acid alleviates septic acute respiratory distress syndrome in mice by suppressing the bronchial epithelial RAS-mediated ferroptosis

in-vivo,

Sepsis,

*GPx4↑, RA notably inhibited the infiltration into the lungs of neutrophils and monocytes with increased amounts of GPX4 and ACE2 proteins, lung function improvement,
*Inflam↓, decreased inflammatory cytokines levels and ER stress in LPS-induced ARDS in mice.
*ER Stress↓,
*Ferroptosis↓, the anti-ferroptosis effect of RA in LPS-induced septic
*Sepsis↓,
*GRP78/BiP↓, Previously, we reported that RA markedly ameliorated septic-associated mortality and lung injury via inhibiting GRP78/IRE1α/JNK pathway-mediated ERS
*IRE1↓,
JNK↓,

3039-

RosA,

Rosmarinic acid liposomes suppress ferroptosis in ischemic brain via inhibition of TfR1 in BMECs

in-vivo,

Nor,

mice

in-vivo,

Stroke,

*Ferroptosis↓, RosA-LIP inhibited ferroptosis by ameliorating mitochondrial abnormalities, increasing GPX4 levels, and decreasing ACSL4/LPCAT3/Lox-dependent lipid peroxidation.
*GPx4↑,
*ACSL4↓,
*BBB↑, RosA-LIP effectively improved blood‒brain barrier (BBB) permeability, increased tight junctions (TJs) protein expression
*IronCh↑, reduced iron levels in ischemic tissue and brain microvascular endothelial cells (BMECs) by modulating FPN1 and TfR1 levels.
*TfR1/CD71↓, Furthermore, RosA-LIP suppressed TfR1 to attenuate ACSL4/LPCAT3/Lox-mediated ferroptosis in TfR1EC cKO mice subjected to dMCAO.
*neuroP↑, proposed neuroprotection of RosA-LIP during ischemic stroke.

4613-

Se,

Rad,

Effect of Selenium and Selenoproteins on Radiation Resistance

Review,

Nor,

*selenoP↑, GPX1 is a selenoprotein with an active site containing selenocysteine
*GPx1↑,
*GPx4↑, GPX4 effectively inhibits lipid peroxide, it also promotes DNA repair
*lipid-P↓,
*DNAdam↓,
*ROS↓, It has been reported that selenium and selenoproteins can scavenge ROS directly.
*radioP↑, selenium and selenium protein as radiation protective agents to alleviate multiple organ damage caused by radiation or treat related diseases.

3313-

SIL,

Silymarin attenuates post-weaning bisphenol A-induced renal injury by suppressing ferroptosis and amyloidosis through Kim-1/Nrf2/HO-1 signaling modulation in male Wistar rats

in-vivo,

NA,

50-100 mg/kg/day

Twenty-four male Wistar rats

*NRF2↑, silymarin activates the Nrf2/HO-1 pathway, thus providing cellular defense
*HO-1↑,
*creat↓, Silymarin diminished BPA-induced rise in serum urea, creatinine, BUN, and plasma kim-1 levels.
*BUN↓,
*RenoP↑, improved renal histoarchitecture in BPA-exposed rats.
*MDA↓, suppression of BPA-induced rise in renal iron, MDA, TNF-α, IL-1β, and cytochrome c levels, and myeloperoxidase and caspase 3 activities by silymarin therapy.
*TNF-α↓,
*IL1β↓,
*Cyt‑c↓,
*Casp3↓,
*GSTs↓, silymarin attenuated BPA-induced downregulation of Nrf2 and GSH levels, and HO-1, GPX4, SOD, catalase, GST, and GR activities.
*GSH↑,
*GPx4↑,
*SOD↑,
*GSR↓,
*Ferroptosis↓, silymarin mitigated post-weaning BPA-induced renal toxicity by suppressing ferroptosis and amyloidosis through Kim-1/Nrf2/HO-1 modulation.

4727-

SSE,

Selenium inhibits ferroptosis in ulcerative colitis through the induction of Nrf2/Gpx4

in-vivo,

Col,

experimental colitis in mice treated with dextran sulfate sodium (DSS)

*Ferroptosis↓, Selenium can relieve DSS-induced colitis and inhibit IECs ferroptosis by up-regulating the expression of Nrf2/Gpx4.
*NRF2↑,
*GPx4↑,
*eff↑, The in vivo results showed that selenium treatment could improve IECs colitis induced by DSS and inhibit ferroptosis.
*other↓, The serum selenium content of UC patients was lower than that of healthy subjects.
*antiOx↑, Selenium, an essential micronutrient of human, which has the functions of anti-oxidation, immune regulation, anti-inflammatory and anti-tumor
*Inflam↓,
AntiTum↑,

4732-

SSE,

Selenium inhibits ferroptosis and ameliorates autistic-like behaviors of BTBR mice by regulating the Nrf2/GPx4 pathway

in-vivo,

Autism,

BTBR mice

*Ferroptosis↓, Selenium inhibits ferroptosis and ameliorate abnormal behavior via the Nrf2/Gpx4 signaling pathway.
*NRF2↑, Treatment with Se increased levels of Nrf2 and GPX4.
*GPx4↑,
*other↝, Se exhibited a beneficial effect on autism-relevant behaviors and inhibited ferroptosis in the BTBR mouse model of ASD, possibly through modulation of the Nrf2/GPX4 signaling pathway.

5094-

SSE,

Sodium Selenite Prevents Matrine-Induced Nephrotoxicity by Suppressing Ferroptosis via the GSH-GPX4 Antioxidant System

vitro+vivo,

Nor,

NRK52E

explored the involvement of ferroptosis in MT-induced kidney injury and evaluated the potential efficacy and underlying mechanism of sodium selenite (SS) in attenuating MT-induced nephrotoxicity.

*GPx4↑, SS also reversed the MT-induced reduction in GPX4, CTH and xCT protein levels.
*xCT/SLC7A11↑,
*GSH↑, SS is a promising therapeutic drug for alleviating MT-induced renal injury by activating the GSH-GPX4 axis.
*RenoP↑,

3405-

TQ,

doxoR,

Protective effect of thymoquinone against doxorubicin-induced cardiotoxicity and the underlying mechanism

vitro+vivo,

NA,

mice

*cardioP↑, thymoquinone can alleviate doxorubicin-induced cardiac toxicity in mice.
*NRF2↑, alleviate iron death in mouse cardiomyocytes by activating the Nrf2/HO-1 signaling pathway
*HO-1↑,
*ROS↓, Thymoquinone can also alleviate oxidative stress in mouse cardiomyocytes
*NQO1↑, similar effects on the expression levels of NQO1, COX-2, and NOX4
*COX2/PTGS2↓, implied
*NOX4↓, implied
*GPx4↑,
*FTH1↑, Reduces free iron, limiting ferroptosis
*p‑mTOR↓,
*TGF-β↓,

1215-

VitC,

immuno,

Metabolomics reveals ascorbic acid inhibits ferroptosis in hepatocytes and boosts the effectiveness of anti-PD1 immunotherapy in hepatocellular carcinoma

ex-vivo,

HCC,

in-vivo,

HCC,

mice

other↓, AA in vivo experiments demonstrated a reduction in liver injury in mice
*GPx4↑,
*GSH↑,
GPx4↓,
GSH↓,
selectivity↑, Based on different the and gpx4 response for normal vs cancer cells

7887-

VT,

IVT,

Dietary Flavonoids Vitexin and Isovitexin: New Insights into Their Functional Roles in Human Health and Disease Prevention

Review,

AD,

Review,

Var,

*antiOx↑, antioxidant, anti-inflammatory, anticancer, antibacterial, and neuroprotective mechanisms.
*Inflam↓,
*AntiCan↑,
*Bacteria↓,
*neuroP↑, cardiovascular protection, blood sugar regulation, anti-obesity, anticancer, antioxidant, anti-inflammatory, and neuroprotective properties.
*Obesity↓,
*cardioP↑, Vitexin exerts a cardioprotective effect against DOX-induced cardiac toxicity by reducing oxidative stress, lowering cardiac inflammatory cytokines, increasing FOXO3a, and inhibiting caspase-3 activation.
*ROS↓, Sprague-Dawley rat hearts, H9c2 cells 10 μM Reducing ROS levels; improving mitochondrial activity, mitochondrial membrane potential, and ATP content; markedly increasing MFN2 expression and reducing the recruitment of Drp1 in mitochondria.
*MMP↑,
*ATP↑,
*MFN2↑,
*DRP1/DNM1L↓,
*FOXO3↑, Protect against DOX-induced acute cardiotoxicity Rats 30 mg/kg Vitexin induced elevated FOXO3a protein expression levels, by suppressing oxidative stress
*NRF2↑, vitexin activated nuclear factor-erythroid 2-related factor 2 (Nrf2) in HUVEC under high glucose.
*Ferroptosis↓, Diabetic nephropathy HK-2 cells/DN rat 0–40 μM Vitexin could alleviate diabetic nephropathy by attenuated ferroptosis via activating GPX4
*GPx4↑,
TumCP↓, Gastric cancer Nude mice/GC cells 2 mg/kg 10–160 μM Vitexin inhibited the malignant progression of GC in vitro and in vivo by suppressing HMGB1-mediated activation of PI3K/Akt/HIF-1α signaling pathway.
HMGB1↓,
PI3K↓,
Akt↓,
Hif1a↓,
CDK1↓, Colon cancer HCT-116 cells 1–300 μM Inhibit colon cancer HCT-116 cell proliferation by suppressing CDK1/cyclin B expression, leading to cell cycle arrest in the G2/M phase.
CycB/CCNB1↓,
TumCCA↑,
Apoptosis↑, Isovitexin Colon cancer Promoted apoptosis and suppressed cell proliferation by activating the p53 signaling pathway.
P53↑,
NF-kB↓, Non-small cell lung cancer cells A549/ H1299 cells, nude mice 1–120 μM Suppressed NF-κB, AKT and ERK activation. [24] Vitexin A549 cells, nude mice 0–40 μM Reduced the levels of p-PI3K, p-Akt, and p-mTOR.
ERK↓,
p‑PI3K↓,
miR-34a↑, Isovitexin Hepatocarcinoma SK-Hep-1 cells Mediated miR-34a upregulation induces apoptosis and suppresses the stemness of SK-SC.
Apoptosis↑,
CSCs?,
*MAPK↓, Isovitexin Acute lung injury RAW 264.7 cells 0–50 μM Inhibiting MAPK and NF-κB and activating HO-1/Nrf2 pathways.
*HO-1↑,
*hepatoP↑, EAH mice 5 mg/kg Vitexin ameliorated hepatic injury in EAH mice through activation of the AMPK/AKT/GSK-3β pathway and upregulation of the Nrf2 gene.
*AMPK↑,
*Akt↑,
*GSK‐3β↑,
*chemoP↑, Vitexin exerts a cardioprotective effect against DOX-induced cardiac toxicity by reducing oxidative stress, lowering cardiac inflammatory cytokines, increasing FOXO3a, and inhibiting caspase-3 activation.
*Casp3↓,
*IRes↝, Vitexin and isovitexin flavonoids not only affected the absorption of peripheral glucose in insulin and non-insulin sensitive tissues but also showed the potential to restore insulin resistance in HepG2 cells by enhancing cellular uptake of glucose.
*GlucoseCon↑,
ChemoSen↑, When combined with doxorubicin (Dox), vitexin can reduce tumor growth and show synergistic effects in in vivo tests, increasing antitumor efficacy.
*GSH↑, Vitexin also increased Nrf2 expression and boosted GSH and antioxidant enzymes such as SOD, CAT, GPx, and GST.
*SOD↑,
*ATF2↑,
*GPx↑,
*GSTs↑,
*AntiAge↑, In Caenorhabditis elegans, studies have shown that vitexin and isovitexin, as putative SKN-1/Nrf2 activators, increase lifespan and support a healthy lifespan.
*Stroke↓, It has been demonstrated that vitexin protects against a cerebral ischemia/reperfusion (I/R)-induced increase in the permeability of brain endothelial cells
*AChE↓, vitexin treatment significantly inhibited acetylcholinesterase activity and markedly downregulated the expression of ace-1 and ace-2.
*ACE/ACE1↓,
*ACE2↓,
*GutMicro↑, Vitexin and isovitexin have also shown promising potential in modulating intestinal microbiota and in turn play a significant role in regulating various diseases such as overweight
*MPO↓, Vitexin can also resist Helicobacter pylori infection, which may be related to its anti-myeloperoxidase (MPO) enzyme activity and inhibition of H- and K-ATPase activity
*H+/K+-ATPase↓,
*AntiDiabetic↑, Antidiabetic Vitexin and Isovitexin Inhibits α-glucosidase/α-amylase, promotes GLUT4, modulates gut microbiota
*GLUT4↑,
*Obesity↓, Anti-obesity Vitexin Activates AMPKα, inhibits C/EBPα, FAS, activates Hedgehog signaling
*HH↓,
*RenoP↑, vitexin protects the kidneys and prevents the formation of kidney stones by inhibiting pyroptosis, apoptosis, epithelial–mesenchymal transition (EMT), and macrophage activation.
*BioAv↓, Vitexin and isovitexin have poor absorption in the gastrointestinal tract, with significant first-pass effects in the intestine (approximately 94%), stomach (30%), and liver (50%), resulting in a lower bioavailability (F) (approximately 5%).
*BioAv↝, The absorption and metabolism processes of vitexin and isovitexin in the human body are complex, and their bioavailability is influenced by multiple factors, including the action of the gut microbiota, interactions with dietary components, first-pass
*BioAv↑, The vitexin-loaded bilayer nanoparticles are designed by assembling soybean peptides and coating them with a goblet cell-targeting peptide. They significantly increase the bioaccessibility and bioavailability of vitexin

Showing Research Papers: 1 to 21 of 21

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 21

Pathway results for Effect on Cancer / Diseased Cells:

Functional Outcomes(tgid=23) ⓘ

AntiCan↑, 1, AntiTum↑, 1,
Total Targets: 50

Pathway results for Effect on Normal Cells:

NA, unassigned(tgid=0) ⓘ

ACE/ACE1↓, 1, ACE2↓, 1, H+/K+-ATPase↓, 1, IRes↝, 1, Stroke↓, 2,

Redox & Oxidative Stress(tgid=1) ⓘ

4-HNE↓, 1, antiOx↑, 4, Catalase↑, 5, Ferroptosis↓, 10, GPx↑, 2, GPx1↑, 6, GPx4↑, 19, GSH↑, 6, GSR↓, 1, GSTs↓, 1, GSTs↑, 1, HO-1↑, 4, i-Iron↓, 2, lipid-P↓, 3, MDA↓, 4, MFN2↑, 1, MPO↓, 1, NOX4↓, 1, NQO1↑, 1, NRF2↑, 9, OXPHOS↓, 2, ROS↓, 9, mt-ROS↓, 1, selenoP↑, 1, SOD↑, 7, SOD1↑, 4, SOD2↑, 2, TAC↑, 1, xCT/SLC7A11↑, 3,

Metal & Cofactor Biology(tgid=2) ⓘ

Ferritin↑, 1, FTH1↑, 1, IronCh↑, 1, TfR1/CD71↓, 1,

Mitochondria & Bioenergetics(tgid=3) ⓘ

ATP↑, 1, DRP1/DNM1L↓, 1, mitResp↓, 1, MMP↑, 1, MMP↝, 1, mtDam↓, 2,

Core Metabolism/Glycolysis(tgid=4) ⓘ

ACSL4↓, 3, AMPK↑, 1, BUN↓, 1, GlucoseCon↑, 1, Glycolysis↑, 2, HK2↑, 2, LDH↑, 1, PFKL↑, 2, PFKM↑, 2, PFKP↑, 1, PKM2↑, 2,

Cell Death(tgid=5) ⓘ

Akt↑, 1, Apoptosis↓, 1, ATF2↑, 1, Casp3↓, 2, Cyt‑c↓, 1, Ferroptosis↓, 10, MAPK↓, 1,

Transcription & Epigenetics(tgid=7) ⓘ

other↓, 1, other↑, 1, other↝, 2, tumCV↑, 1,

Protein Folding & ER Stress(tgid=8) ⓘ

ER Stress↓, 1, GRP78/BiP↓, 1, IRE1↓, 1,

DNA Damage & Repair(tgid=10) ⓘ

DNAdam↓, 1,

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

FOXO3↑, 1, GSK‐3β↑, 1, HH↓, 1, p‑mTOR↓, 1, TRPM7↓, 1,

Migration(tgid=13) ⓘ

5LO↓, 1, CD31/PECAM-1↑, 1, PKCδ↑, 1, TGF-β↓, 1, TumCMig↑, 1,

Angiogenesis & Vasculature(tgid=14) ⓘ

angioG↑, 1,

Barriers & Transport(tgid=15) ⓘ

BBB↑, 2, GLUT1↑, 2, GLUT4↑, 2,

Immune & Inflammatory Signaling(tgid=16) ⓘ

COX2/PTGS2↓, 2, IL1β↓, 2, IL1β↑, 1, Inflam↓, 5, NF-kB↑, 1, TLR4↓, 1, TNF-α↓, 2,

Cellular Microenvironment(tgid=17) ⓘ

pH↑, 1,

Synaptic & Neurotransmission(tgid=18) ⓘ

AChE↓, 2, BDNF↑, 1,

Drug Metabolism & Resistance(tgid=21) ⓘ

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

Clinical Biomarkers(tgid=22) ⓘ

BloodF↑, 1, creat↓, 1, Ferritin↑, 1, GutMicro↑, 1, LDH↑, 1,

Functional Outcomes(tgid=23) ⓘ

AntiAge↑, 1, AntiCan↑, 1, AntiDiabetic↑, 1, cardioP↑, 4, chemoP↑, 1, cognitive↑, 2, hepatoP↑, 1, memory↑, 1, neuroP↑, 5, Obesity↓, 2, radioP↑, 1, RenoP↑, 3, toxicity?, 1, toxicity∅, 1, Wound Healing↑, 1,

Infection & Microbiome(tgid=24) ⓘ

Bacteria↓, 1, Sepsis↓, 1,
Total Targets: 122

Scientific Paper Hit Count for: GPx4, Glutathione Peroxidase 4

5 Magnetic Fields
3 Selenite (Sodium)
2 doxorubicin
2 Rosmarinic acid
1 Artemisinin
1 Carvacrol
1 Formononetin
1 Honokiol
1 Hyperoside
1 Isoliquiritigenin
1 Magnetic Field Rotating
1 Selenium
1 Radiotherapy/Radiation
1 Silymarin (Milk Thistle) silibinin
1 Thymoquinone
1 Vitamin C (Ascorbic Acid)
1 immunotherapy
1 Vitexin
1 Isovitexin

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

GPx4 Cancer Research Results

Pathway results for Effect on Cancer / Diseased Cells:

Redox & Oxidative Stress(tgid=1) ⓘ

Metal & Cofactor Biology(tgid=2) ⓘ

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) ⓘ

Immune & Inflammatory Signaling(tgid=16) ⓘ

Drug Metabolism & Resistance(tgid=21) ⓘ

Functional Outcomes(tgid=23) ⓘ

Pathway results for Effect on Normal Cells:

NA, unassigned(tgid=0) ⓘ

Redox & Oxidative Stress(tgid=1) ⓘ

Metal & Cofactor Biology(tgid=2) ⓘ

Mitochondria & Bioenergetics(tgid=3) ⓘ

Core Metabolism/Glycolysis(tgid=4) ⓘ

Cell Death(tgid=5) ⓘ

Transcription & Epigenetics(tgid=7) ⓘ

Protein Folding & ER Stress(tgid=8) ⓘ

DNA Damage & Repair(tgid=10) ⓘ

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

Migration(tgid=13) ⓘ

Angiogenesis & Vasculature(tgid=14) ⓘ

Barriers & Transport(tgid=15) ⓘ

Immune & Inflammatory Signaling(tgid=16) ⓘ

Cellular Microenvironment(tgid=17) ⓘ

Synaptic & Neurotransmission(tgid=18) ⓘ

Drug Metabolism & Resistance(tgid=21) ⓘ

Clinical Biomarkers(tgid=22) ⓘ

Functional Outcomes(tgid=23) ⓘ

Infection & Microbiome(tgid=24) ⓘ

Home Page