Database Query Results : , , Trx

Trx, Thioredoxin: Click to Expand ⟱

Source:

Type: protein

Trx is a small protein that acts as a reducing agent, donating electrons to reduce oxidized proteins and other molecules.
Trx is overexpressed in various types of cancer, including breast, lung, colon, and prostate cancer.

- Cytosolic thioredoxin (TRX-1) and mitochondrial thioredoxin (TRX-2).

- Thioredoxin is a pivotal redox regulator that protects cells from oxidative stress and supports survival and proliferation.

- There is interest in combining thioredoxin inhibitors with conventional chemotherapy or radiotherapy to sensitize tumors to oxidative stress and improve treatment efficacy.

Scientific Papers found: Click to Expand⟱

2394-

CAP,

Capsaicin acts as a novel NRF2 agonist to suppress ethanol induced gastric mucosa oxidative damage by directly disrupting the KEAP1-NRF2 interaction

in-vitro,

Nor,

GES-1

(0, 2, and 8 μM)

*mtDam↓, CAP ameliorated mitochondrial damage, facilitated the nuclear translocation of NRF2, thereby promoting the expression of downstream antioxidant response elements, HO-1, Trx, GSS and NQO1 in GES-1 cells.
*NRF2↑,
*HO-1↑,
*Trx↑,
*GSS↑,
*NQO1↑,
*Keap1↓, CAP could directly bind to KEAP1 and inhibit the interaction between KEAP1 and NRF2.
*ROS↓, Capsaicin protects GES-1 from oxidative stress
*PKM2↓, Previous studies have demonstrated that CAP can directly bind to and inhibit the activity of PKM2 and LDHA, subsequently attenuating inflammatory response
*LDHA↓,
*Inflam↓,

1978-

CUR,

Curcumin targeting the thioredoxin system elevates oxidative stress in HeLa cells

in-vitro,

Cerv,

HeLa

TrxR1↓, curcumin can target the cytosolic/nuclear thioredoxin system to eventually elevate oxidative stress in HeLa cells
ROS↑,
DNA-PK↑, subsequently induces DNA oxidative damage
eff↑, curcumin-pretreated HeLa cells are more sensitive to oxidative stress
Trx↓, down-regulates Trx1 level and decreases Trx activity in HeLa cells
Trx1↓,

642-

EGCG,

Prooxidant Effects of Epigallocatechin-3-Gallate in Health Benefits and Potential Adverse Effect

ROS↑, under high-dose conditions. Autooxidation of EGCG generates substantial ROS
H2O2↑, One EGCG molecule could produce more than two H2O2 molecules
Apoptosis↑,
Trx↓, High concentration of EGCG inactivated Trx/TrxR via the formation of EGCG-Trx1 and EGCG-TrxR conjugates
TrxR↓, High concentration of EGCG inactivated Trx/TrxR via the formation of EGCG-Trx1 and EGCG-TrxR conjugates
JNK↑,
HO-1↑,
Fenton↑,

1975-

EGCG,

Molecular bases of thioredoxin and thioredoxin reductase-mediated prooxidant actions of (-)-epigallocatechin-3-gallate

in-vitro,

Cerv,

HeLa

TrxR↓, EGCG-induced inactivation of TrxR and decreased cell survival, revealing TrxR as a new target of EGCG.
Trx↓,
ROS↑, EGCG induced inactivation of Trx/TrxR in parallel with increased ROS levels in HeLa cells.
Dose↑, Statistics indicated that ROS levels were significantly higher within a range of 50-200uM EGCG than that at 25 uM EGCG, but there were no significant differences in ROS levels between 50 uM vs 100 uM,

1955-

GamB,

Gambogic acid inhibits thioredoxin activity and induces ROS-mediated cell death in castration-resistant prostate cancer

in-vitro,

Pca,

PC3

185nM

in-vitro,

Pca,

LNCaP

in-vitro,

Pca,

DU145

ROS↑, GA disrupted cellular redox homeostasis, observed as elevated reactive oxygen species (ROS), leading to apoptotic and ferroptotic death.
Apoptosis↑,
Ferroptosis↑,
Trx↓, GA inhibited thioredoxin
eff↑, Auranofin (AUR), a thioredoxin reductase (TrxR) inhibitor was the one compound that demonstrated additive growth inhibition together with GA when both were combined at sub-thresh hold concentrations
TrxR↓, GA may inhibit the thioredoxin (Trx) system, which mainly composes NADPH, TrxR, and Trx.
Dose∅, GA demonstrated sub-micromolar activity (IC50 = 185nM) which was 50 times more potent than the next most active compounds, curcumin and tanshinone (CT)
MMP↓, GA treatment showed increasing loss of membrane polarity at 4 and 6 hours in PCAP-1 cells
eff↑, GA enhanced the cell killing observed for either docetaxel (DOX) or enzalutamide (ENZA)
Casp↑, These results suggest that GA initiates CASP-dependent death of PCAP-1 cells and that both iron-dependent oxidative injury and direct CASP activation contribute
NADPH↓, These results suggest that GA may inhibit the thioredoxin (Trx) system, which mainly composes NADPH, TrxR, and Trx.
TrxR↓,
ChemoSen↑, potential use of GA in combination with standard chemotherapeutic (docetaxel) and anti-androgen endocrine (enzalutamide) therapies for advanced PrCa.
AR↓, inhibit PrCa growth, in part by inhibiting AR signaling

1973-

GamB,

Gambogic acid deactivates cytosolic and mitochondrial thioredoxins by covalent binding to the functional domain

in-vitro,

Liver,

SMMC-7721 cell

Apoptosis↑, selectively induces apoptosis in cancer cells, at least partially, by targeting the stress response to reactive oxygen species (ROS).
ROS↑,
Trx↓, deactivates TRX-1/2 proteins by covalent binding to the active cysteine residues in the functional domain via Michael addition reactions.
Trx1↓,
Trx2↓,
Mich↑, can react with small nucleophilic molecules, such as GSH and a cysteine-containing peptide, via a Michael addition reaction.

4513-

GLA,

Antineoplastic Effects of Gamma Linolenic Acid on Hepatocellular Carcinoma Cell Lines

in-vitro,

Liver,

HUH7

TumCP↓, GLA treatment significantly reduced cell proliferation, generated ROS, and induced apoptosis.
ROS↑, The ROS levels were increased 3.4-fold by 3 h exposure to GLA compared to the control
Apoptosis↑,
HO-1↑, antioxidant proteins to be upregulated: heme oxygenase-1 (HO-1), aldo-keto reductase 1 family C1 (AKR1C1), C4 (AKR1C4), and thioredoxin (Trx).
Trx↑,
lipid-P↑, GLA treatment has induced cell growth inhibition, ROS generation including lipid peroxidation, and HO-1 production for antioxidant protection against oxidative stress caused by GLA in Huh7 cells.
eff↓, Our study showed that the cytotoxic effect of GLA was almost blocked when the Huh7 cells were supplemented with Vitamin E in addition to GLA.
MMP↓, decreased mitochondrial membrane potential was observed in our study.
DNAdam↑, we observed DNA fragmentation in Huh7 cells under GLA expose.
selectivity↑, We had observed that no cytotoxicity of primary cultured hepatocytes from rat liver was observed in a concentration of GLA of 250 µM

2902-

HNK,

Rad,

Honokiol Mitigates Ionizing Radiation-Induced Injury by Maintaining the Redox Balance of the TrxR/Trx System

in-vitro,

Nor,

BEAS-2B

*TrxR1↑, HKL pre-exposure significantly increased the expressions of TrxR1 and Trx proteins in general, in particular at doses ranging between 0.05 and 5 µM HKL
*Trx↑,
*radioP↑, Overall, the findings presented here demonstrate that HKL has the potential to be a novel radioprotector capable of cellular protection against radiation-induced injuries
*ROS↓, Compared to the IR group, there was a significant decrease in the ROS levels of the HKL+IR treated group

2255-

MF,

Pulsed Electromagnetic Fields Induce Skeletal Muscle Cell Repair by Sustaining the Expression of Proteins Involved in the Response to Cellular Damage and Oxidative Stress

in-vitro,

Nor,

SkMC

1.5 mT PEMF for four hours repeated for two days

*HSP70/HSPA5↑, HSP70), which can promote muscle recovery, inhibits apoptosis and decreases inflammation in skeletal muscle, together with thioredoxin, paraoxonase, and superoxide dismutase (SOD2), which can also promote skeletal muscle regeneration following injury
*Apoptosis↓,
*Inflam↓,
*Trx↓,
*PONs↓, Paraoxonase 2 (PON2, Paraoxonase 3 (PON3) (+19% vs. controls)
*SOD2↓,
*TumCG↑, PEMF treatment enhanced muscle cell proliferation by approximately 20% both in cells grown in complete medium
*Diff↑, suggest the potential role of PEMF in the induction of muscle differentiation
*HIF2a↑, hypoxia-inducible transcription factor 2a (HIF-2a) (+40% vs. controls),
*Cyt‑c↑, Cytochrome c (+39% vs. controls)
P21↑, p21/CIP1 (+27% vs. controls)

2649-

PL,

Oxidative Stress Inducers in Cancer Therapy: Preclinical and Clinical Evidence

Review,

Var,

AntiCan↑, investigated for its anticancer activity in various cancer types, including hematological cancers, colorectal, gastric, lung, breast, prostate, and oral cancers, melanoma, and glioma
ROS↑, Its in vitro anticancer activity can be attributed to induction of ROS through increased glutathione disulfide levels, decreased glutathione levels
GSH↓,
TrxR↓, inhibition of thioredoxin reductase (TrxR), an enzyme which reduces thioredoxin, a redox protein that protects against oxidative stress
Trx↓,
Apoptosis↑, PPL-mediated ROS accumulation further leads to ROS-mediated apoptosis
TumCCA↑, G1 or G2/M cell cycle arrest
ER Stress↑, ER stress
DNAdam↑, oxidative DNA damage
ChemoSen↑, PPL was reported to sensitize head and neck, gastric, and liver cancers to cisplatin [18], oxaliplatin [19], and sorafenib [20], respectively
BioAv↓, Additionally, its poor aqueous solubility and bioavailability limit its therapeutic potential

2950-

PL,

Overview of piperlongumine analogues and their therapeutic potential

Review,

Var,

AntiAg↑, PL has been shown to exert in vitro antiplatelet aggregation effect induced by agonists such as collagen, adenosine 50-diphosphate (ADP), arachidonic acid (AA) and thrombin.
neuroP↑, Neuroprotective activity of PL and its derivatives
Inflam↓, Anti-inflammatory activity of PL and its derivatives
NO↓, production of NO and PGE2 was significantly inhibited after the treatment of PL.
PGE2↓,
MMP3↓, PL also significantly suppressed the production of MMP-3 and MMP-13
MMP13↓,
TumCMig↓, PL inhibited the proliferation, induced the apoptosis and reduced the migration and invasion of RA FLS by activating the p38, JNK, NF-kB and STAT3 pathways
TumCI↓,
p38↑,
JNK↑,
NF-kB↑,
ROS↑, PL has been reported to selectively induce apoptotic by ROS accumulation in cancer cells via different molecular mechanisms.
FOXM1↓, PL inhibited proteasome including suppression of FOXM1
TrxR1↓, induction of ROS by directly inhibiting thioredoxin reductase 1 (TrxR1) activity
GSH↓, Wang et al. demonstrated that PL could inhibit both glutathione and thioredoxin and thus induce ROS elevation,
Trx↓,
cMyc↓, downregulation of c-Myc and LMP1 and the Caspase-3-dependent apoptosis of Burkitt lymphoma cells in vitro.
Casp3↑,
Bcl-2↓, PL could downregulate Bcl-2 and Mcl-1 and decrease the expression of STAT-3
Mcl-1↓,
STAT3↓, Bharadwaj et al. identiï¬ed PL as a direct STAT3 inhibitor
AR↓, Golovine et al. demonstrated for the ï¬rst time that PL rapidly reduced the androgen receptor protein level of prostate cancer cells
DNAdam↑, inducing DNA damage,

2962-

PL,

Synthesis of Piperlongumine Analogues and Discovery of Nuclear Factor Erythroid 2‑Related Factor 2 (Nrf2) Activators as Potential Neuroprotective Agents

in-vitro,

Nor,

PC12

*GSH↑, compounds 4 and 5 remarkably elevats GSH level and antioxidant enzymes activity (NQO1, Trx, and TrxR).
*NQO1↑,
*Trx↑,
*TrxR↑,
*NRF2↑, revealed that the total Nrf2 expression was slightly upregulated. 4 and 5, have been identiﬁed as potent Nrf2 activators with minimal cytotoxicity.
*NRF2⇅, Notably, the cytosolic Nrf2 decreased gradually (Figure 9, middle panel). Coincidently, the amount of Nrf2 in nuclei increased.
*eff↑, Induction of transcription of antioxidant genes via the Nrf2-dependent cytoprotective pathway requires translocation of Nrf2 from cytosol to nucleus.
*BioAv↑, PL could cross the BBB after oral administration
*ROS↓, The elevation of cellular endogenous antioxidant system prevents the accumulation of ROS and thus confers protection against oxidative insults to the cells.

1985-

PTL,

KEAP1 Is a Redox Sensitive Target That Arbitrates the Opposing Radiosensitive Effects of Parthenolide in Normal and Cancer Cells

in-vitro,

Pca,

LNCaP

in-vitro,

Pca,

DU145

in-vitro,

Nor,

PrEC

in-vivo,

NA,

mice

ROS↑, parthenolide enhances ROS production in prostate cancer cells through activation of NADPH oxidase
NADPH↑,
RadioS↑, In vivo, parthenolide increases radiosensitivity of mouse xenograft tumors but protects normal prostate and bladder tissues against radiation-induced injury
radioP↑, DMAPT, the water soluble prodrug of parthenolide, is a promising agent for selectively enhancing the sensitivity of prostate cancer cells to radiation while protecting normal tissues from damage caused by radiation.
Trx↓, causes oxidation of thioredoxin (TrX) in prostate cancer cells
*ox-Keap1↑, three normal cell lines, parthenolide increased the oxidized form of Keap1 but decreased the reduced form of Keap1
ox-Keap1↓, results from the three cancer cell lines appeared to be completely opposite to results observed in normal cells treated with parthenolide
rd-Keap1↑, in vivo results show that parthenolide decreased the oxidized form of Keap1 but increased the reduced form of Keap1 in the tumors
*NRF2↑, Oxidization of Keap1 leads to activation of the Nrf2 pro-survival pathway in normal cells. Nrf2 pathway is a major mechanism by which parthenolide protects normal cells against radiation injury
NRF2∅, but no changes were observed in the three cancer cell lines.
NF-kB↓, It has been reported that parthenolide is a potent inhibitor of NF-κB

1986-

PTL,

Modulation of Cell Surface Protein Free Thiols: A Potential Novel Mechanism of Action of the Sesquiterpene Lactone Parthenolide

in-vitro,

NA,

JNK↑, parthenolide mediated activation of JNK
ROS↑, parthenolide induced generation of intracellular reactive oxygen species
eff↓, Parthenolide Cytotoxicity Is Blocked by Thiol Antioxidants
NF-kB↓, parthenolide has been shown to induce malignant cell death by inhibiting NFκB activation and/or activating JNK
Trx↓, thioredoxin pull-down

1987-

PTL,

Rad,

A NADPH oxidase dependent redox signaling pathway mediates the selective radiosensitization effect of parthenolide in prostate cancer cells

in-vitro,

Pca,

PC3

in-vitro,

Nor,

PrEC

selectivity↑, parthenolide (PN), a sesquiterpene lactone, selectively exhibits a radiosensitization effect on prostate cancer PC3 cells but not on normal prostate epithelial PrEC cells.
RadioS↑,
ROS↑, oxidative stress in PC3 cells but not in PrEC cells
*ROS∅, oxidative stress in PC3 cells but not in PrEC cells
NADPH↑, In PC3 but not PrEC cells, PN activates NADPH oxidase leading to a decrease in the level of reduced thioredoxin, activation of PI3K/Akt and consequent FOXO3a phosphorylation, which results in the downregulation of FOXO3a targets, MnSOD, CAT
Trx↓,
PI3K↑,
Akt↑,
p‑FOXO3↓, downregulation of FOXO3a targets, antioxidant enzyme manganese superoxide dismutase (MnSOD) and catalase
SOD2↓, MnSOD
Catalase↓,
radioP↑, when combined with radiation, PN further increases ROS levels in PC3 cells, while it decreases radiation-induced oxidative stress in PrEC cells
*NADPH∅, Parthenolide activates NADPH oxidase in PC3 cells but not in PrEC cells
*GSH↑, increases glutathione (GSH) in PrEC cells(normal cells)
*GSH/GSSG↑, GSH/GSSG ratio is not significantly changed by parthenolide in PC3 cells but is increased 2.4 fold in PrEC cells (normal cells)
*NRF2↑, The induction of GSH may be due to the activation of the Nrf2/ARE (antioxidant/electrophile response element) pathway

4827-

QC,

CUR,

Synthetic Pathways and the Therapeutic Potential of Quercetin and Curcumin

Review,

Var,

*AntiCan↑, their anti-cancer effects, but also with regard to their anti-diabetic, anti-obesity, anti-inflammatory, and anti-bacterial actions.
*Inflam↓,
*Bacteria↓,
*AntiDiabetic↑,
*ROS↓, suppression of ROS formation via the inhibition of the enzyme activities involved in their production, or via scavenging ROS directly by acting as hydrogen donors; the chelation of the metal ions that induce ROS production;
*SOD↑, quercetin can eliminate free radicals and help maintain a stable redox state in cells by increasing anti-oxidant enzymes, such as superoxide dismutase (SOD), and catalase expressions, as well as the level of reduced glutathione (GSH)
*Catalase↑,
*GSH↑,
*NRF2↑, Quercetin can protect human granulosa cells from oxidative stress by inducing Nrf2 expression at both the gene and protein levels, which in turn induces the anti-oxidant thioredoxin (Trx) system.
*Trx↑,
*IronCh↑, pure curcumin, a metal chelator, directly removes ROS and regulates numerous enzymes.
*MDA↑, It has the potential to reduce the concentration of malondialdehyde (MDA) in serum and increase the total anti-oxidant potential
cycD1/CCND1↓, Cyclin D1 expression was significantly decreased in quercetin-treated ovarian SKOV-3 cells, but not in cisplatin (CDDP)-resistant SKOV3/CDDP cells.
PI3K↓, The levels of PI3K and phospho-Akt were decreased in curcumin-treated SKOV3 cells, which in turn increased caspase-3 and Bax levels.
Casp3↑,
BAX↑,
ChemoSen↑, Curcumin enhanced the efficacy of chemotherapy in colorectal cancer cells.
ROS↑, suggesting that quercetin-induced cytotoxicity and autophagy were initiated by the generation of ROS
eff↑, quercetin or curcumin with chemotherapeutic agents, as shown below, considerably enhances the antitumor potencies of doxorubicin (DOX) and cisplatin.
MMP↓, The synergistic treatment with curcumin and quercetin inhibited the cell proliferation associated with the loss of mitochondrial membrane potential (ΔΨm), the release of cytochrome c, a decrease in AKT and ERK phosphorylation in MGC803 human gastric
Cyt‑c↑,
Akt↓,
ERK↓,

3068-

RES,

Resveratrol decreases the expression of genes involved in inflammation through transcriptional regulation

in-vitro,

lymphoma,

U937

p65↓, In our study, RESV treatment significantly decreased p65 expression and reduced the activities of the antioxidant enzymes SOD2, PRX2, CAT, and TRX.
SOD2↓,
Prx↓,
Catalase↓,
Trx↓,
TNF-α↓, (i.e., TNF-α, IL-8, and MCP-1), whereas a reduction in the protein levels of these cytokines was observed in the presence of RESV.
IL8↓,
MCP1↓,
SIRT1↑, a trend of increased SIRT1 activity in the presence of RESV was observed, which may be due to the low dose of RESV used

3026-

RosA,

Modulatory Effect of Rosmarinic Acid on H2O2-Induced Adaptive Glycolytic Response in Dermal Fibroblasts

in-vitro,

Nor,

0–100 μM

 dermal fibroblasts

*ROS↓, H2O2 caused a significant ROS increase in the cells, and pre-treatment with rosmarinic acid (5–50 µM) decreased ROS significantly in the presence of glutathione
*ATP↑, The rosmarinic acid also recovered intracellular ATP and decreased NADPH production via the pentose phosphate pathway.
*NADPH↓,
*HK2↓, (HK-2), phosphofructokinase-2 (PFK-2), and lactate dehydrogenase A (LDHA), were downregulated in cells treated with rosmarinic acid
*PFK2↓,
*LDHA↓,
*GSR↑, GSR), glutathione peroxidase-1 (GPx-1), and peroxiredoxin-1 (Prx-1) and redox protein thioredoxin-1 (Trx-1) were upregulated in treated cells compared to control cells.
*GPx↑,
*Prx↑,
*Trx↑,
*antiOx↑, To sum up, the rosmarinic acid could be used as an antioxidant against H2O2-induced adaptive responses in fibroblasts by modulating glucose metabolism, glycolytic genes, and GSH production.
*GSH↑, The pre-treatment of rosmarinic acid could raise intracellular GSH to protect cells from ROS
*ROS↓, rosmarinic acid pre-treatment reduced the amount of ROS in the fibroblasts upon the addition of H2O2
*GlucoseCon↓, both compounds also decreased glucose consumption and lactate production
*lactateProd↓,
*Glycolysis↝, The results indicated that rosmarinic acid is able to shape cellular glucose utilization, glycolysis, and GSH.
*ATP↑, The rosmarinic acid also recovered intracellular ATP and decreased NADPH production via the pentose phosphate pathway.
*NADPH↓,
*PPP↓,

4199-

SFN,

Sulforaphane and Brain Health: From Pathways of Action to Effects on Specific Disorders

Review,

AD,

Review,

Park,

*BBB↑, SF is able to cross the blood–brain barrier as well as to protect it
*BDNF↑, SF can protect against neuronal cell death by inhibiting apoptosis, by upregulating brain-derived neurotrophic factor (BDNF) it can enhance neuronal function and plasticity, and support neurogenesis.
*neuroG↑,
*NRF2↑, , Nrf2 inducers like SF that have no direct redox activity are often referred to as “indirect antioxidants”
*HO-1↑, (NQO1) (HO-1 or HMOX), as well as (Cat), (SOD), (Prx), (HSP), glutathione S-transferases (GST), thioredoxin reductase (Trx), glutathione synthetase (GS), glutathione peroxidases (GPx) and glutathione reductase in the brain
*Catalase↑,
*SOD↑,
*HSPs↑, It enhances the expression of HSP70, HSP90, and HSP40 in normal human fibroblasts
*GSTs↑,
*Trx↑,
*GPx↑,
*GSR↑,
*GSH↑, ability of SF to upregulate GSH in the brain is critical for antioxidant protection in youth but may become even more important with age.
*NQO1↑, SF administration to astrocytes increased NQO1 concentrations and protected against oxygen and glucose-induced astrocyte cell death
*GutMicro↑, the fact that SF modulates microbiome composition
*Inflam↓, reduces inflammation and enhances gut barrier integrity,
*neuroP↑, The effect of SF on the gut microbiome may also affect the production of short-chain fatty acids (SCFA) like butyrate, which have neuroprotective effects

2444-

SFN,

Sulforaphane Delays Fibroblast Senescence by Curbing Cellular Glucose Uptake, Increased Glycolysis, and Oxidative Damage

in-vitro,

Nor,

MRC-5

Human fetal lung MRC-5 fibroblasts and human foreskin BJ

*GlucoseCon↓, SFN delayed senescence by decreasing glucose metabolism on the approach to senescence, exhibiting a caloric restriction mimetic-like activity
*ROS↓, and thereby decreased oxidative damage to cell protein and DNA
*Trx↓, This was associated with increased expression of thioredoxin-interacting protein, curbing entry of glucose into cells;
*HK2↓, decreased hexokinase-2
*NRF2↑, SFN is an activator of transcription factor Nrf2 [14] which regulates antioxidant response element- (ARE-) linked gene expression.
*Catalase↑, CAT, PDRX1, and GCLM, expression was increased in senescence and treatment with SFN increased the expression further
*TXNIP↑, increased expression of TXNIP, curbing the entry of glucose into cells
*PFKFB2↓, decreased PFKFB2 and increased G6PD, downregulating glycolysis.
*G6PD↑,

3648-

SIL,

Silymarin/Silybin and Chronic Liver Disease: A Marriage of Many Years

Review,

NA,

*antiOx↑, antioxidant, anti-inflammatory and antifibrotic power
*Inflam↓,
*lipid-P↓, reduce both lipid peroxidation and cellular necrosis.
*necrosis↓,
*hepatoP↑, silybin use in chronic liver diseases, cirrhosis and hepatocellular carcinoma.
*IL1↓, figure 1
*IL6↓,
*TNF-α↓,
*IFN-γ↓,
MAPK↓,
Apoptosis↑,
Cyt‑c↑,
Casp3↑,
Casp9↑,
*PPARγ↑,
*GLUT4↑,
*HSPs↓,
*HSP27↑,
*Trx↑,
*SIRT1↑,
*ALAT↓, as well as prevent ALT increase, Glutathione (GSH) decrease, lipid peroxidation and TNF-α increase
*GSH↑,
*lipid-P↓,
*TNF-α↓,
TumCG↓, silybin significantly reduces HuH7, HepG2, Hep3B, and PLC/PRF/5 human hepatoma cells growth by increasing cyclin-dependent kinase inhibitor p21 and p27/cyclin-dependent kinase (CDK) 4 complexes, by reducing retinoblastoma protein (Rb)-phosphorylatio
P21↑,
CDK4↑,

3302-

SIL,

Protective effects of silymarin in glioblastoma cancer cells through redox system regulation

in-vitro,

GBM,

U87MG

264.6 μM

NRF2↑, The expression level of Nrf2 and HO-1 and glutaredoxin and thioredoxin enzymes were checked by real-time PCR method, and the expression level increased significantly after treatment.
HO-1↑,
Trx↑,
antiOx↑, Our findings suggest that silymarin may exert its cytotoxic and anticancer effects by enhancing the Nrf2/HO-1 pathway through antioxidant mechanisms in U-87 MG cells.

3309-

SIL,

Silymarin as a Natural Antioxidant: An Overview of the Current Evidence and Perspectives

Review,

NA,

*ROS↓, (1) Direct scavenging free radicals and chelating free Fe and Cu are mainly effective in the gut.
*IronCh↑,
*MMP↑, (2) Preventing free radical formation by inhibiting specific ROS-producing enzymes, or improving an integrity of mitochondria in stress conditions, are of great importance.
*NRF2↑, (3) Maintaining an optimal redox balance in the cell by activating a range of antioxidant enzymes and non-enzymatic antioxidants, mainly via Nrf2 activation
*Inflam↓, (4) Decreasing inflammatory responses by inhibiting NF-κB pathways is an emerging mechanism of SM protective effects in liver toxicity and various liver diseases.
*hepatoP↑,
*HSPs↑, (5) Activating vitagenes, responsible for synthesis of protective molecules, including heat shock proteins (HSPs), thioredoxin and sirtuins
*Trx↑,
*SIRT2↑, increased expression of protective molecules (GSH, Thioredoxins, heat shock proteins (HSPs), sirtuins, etc.)
*GSH↑,
*ROS↑, Similarly, production of O2− and NO in isolated rat Kupffer cells were inhibited by silibinin in a dose-dependent manner, with IC50 80 μM
*NADPH↓, It also decreased the NADPH oxidase, iNOS and NF-κB over expression by As and upregulated the Nrf2 expression in the renal tissue.
*iNOS↓,
*NF-kB↓,
*BioAv↓, active free silibinin concentration in plasma after oral consumption of SM, depending on dose of supplementation, could be in the range 0.2–2.0 μM.
*Dose↝, healthy volunteers, after an oral administration of SM (equivalent to 120 mg silibinin), total (unconjugated + conjugated) silibinin concentration in plasma was 1.1–1.3 μg/mL
*BioAv↑, For example, silibinin concentration in the gut could reach 800 μM

4733-

SSE,

Selenium supplementation of lung epithelial cells enhances nuclear factor E2-related factor 2 (Nrf2) activation following thioredoxin reductase inhibition

NA,

Nor,

*selenoP↑, Se is required for the synthesis and function of selenoenzymes including thioredoxin (Trx) reductase-1 (TXNRD1) and glutathione peroxidases (GPx).
*Trx↑,
*GPx↑, TXNRD1 and GPX2 protein expression and enzymatic activity were significantly greater upon Se supplementation
*NRF2↑, Se levels positively influence Nrf2 activation and selenoenzyme responses following TXNRD1 inhibition.

5093-

SSE,

Pharmacological mechanisms of the anticancer action of sodium selenite against peritoneal cancer in mice

in-vivo,

Var,

AntiCan↑, Prior studies in mice show that sodium selenite administered intraperitoneally is highly effective in inhibiting cancer cells implanted in the peritoneal cavity.
eff↑, We found that intraperitoneal delivery of selenite to cancer cells in the peritoneal cavity of mice rapidly and robustly killed the cancer cells, with a therapeutic efficacy higher than that of cisplatin.
selectivity↑, 1) Favorable drug distribution: selenite increased selenium levels in the cancer cells by 250-fold, while in normal tissues only by 7-fold.
ROS↑, 2) Optimal selenium form: selenite was converted in the cancer cells mainly into selenium nanoparticles (SeNPs), which are more efficient than selenite in producing reactive oxygen species (ROS).
Dose↝, we found that the maximum tolerated dose (MTD) of i.p. injection of sodium selenite was 4 mg Se/kg, with no death (Fig. 1A) but marked body weight loss
Trx↓, The powerful effect of i.p. injected selenite is associated with a highly selective Se distribution in favor of intraperitoneal cancer cells, wherein endogenously formed SeNPs efficiently hijack the Trx- and Grx-coupled GSH systems to produce ROS to
GSH↓,

5089-

SSE,

Se,

Redox-mediated effects of selenium on apoptosis and cell cycle in the LNCaP human prostate cancer cell line

in-vitro,

Pca,

LNCaP

ROS↑, Our results demonstrated that oxidative stress was induced by sodium selenite at high concentrations in both acute and chronic treatments, but outcomes were different.
mtDam↑, After acute exposure to selenite, cells exhibited mitochondrial injury and cell death, mainly apoptosis.
TumCD↑,
Apoptosis↑,
TumCCA↑, After chronic exposure to selenite, cells showed growth inhibition caused by cell cycle arrest, increased numbers of mitochondria and levels of mitochondrial enzymes, and only minimal induction of apoptosis
Trx↓, production of ROS, regulation of the Trx redox system, regulation of the cell cycle, and inhibition of angiogenes
angioG↓,
GSH⇅, intracellular levels of GSH were increased at doses of 0.5 and 1.5 uM selenite and decreased at doses of 2 and 2.5 uM selenite
NADPH↓, In addition, GSH and NADPH are consumed
GPx↑, GPX activities in the selenite-adapted cells were significantly increased (2- to 3-fold induction

5084-

SSE,

GEM,

The Antitumor Activity of Sodium Selenite Alone and in Combination with Gemcitabine in Pancreatic Cancer: An In Vitro and In Vivo Study

in-vitro,

PC,

PANC1

5.6uM

vitro+vivo,

PC,

Panc02

 4.6 µM,

C57BL mice bearing a Pan02-generated tumor

tumCV↓, Our results demonstrated a significant inhibition of pancreatic cancer cell viability with the use of sodium selenite alone and a synergistic effect when associated with GMZ
ChemoSen↑,
TumCG↓, combined therapy not only inhibited tumor growth (65%)
OS↑, but also relative to sodium selenite or GMZ used as monotherapy (up to 40%), increasing mice survival.
MMP↓, sodium selenite induced mitochondrial depolarization
AIF↑, sodium selenite induced a large AIF nuclear location in both PANC-1 and Pan02 cells
GSH↓, selenite-mediated depletion of GSH and TRX
Trx↓,
ROS↑, selenite depletes GSH and reduced thioredoxin (TRX-H), leaving the cell defenseless against reactive oxygen species (ROS) and increasing them
AntiTum↑, sodium selenite should be considered as a promising antitumor agent against pancreatic cancer, either alone or in combination with GMZ.

3960-

Taur,

Versatile Triad Alliance: Bile Acid, Taurine and Microbiota

Review,

AD,

Review,

Stroke,

*ROS↓, prevention of oxidative stress, and inflammation.
*Inflam↓,
*GABA↑, It serves as an agonist of GABAA receptors and, through them, exerts its neuronal inhibitory, anxiolytic, and calming effect
*memory↑, Consequently, taurine promotes emotional learning ability, memory, and cognitive performance
*cognitive↑,
*iNOS↓, It reduces inducible nitric oxide synthase (iNOS), C-reactive protein (CRP),
*CRP↓,
*HO-1↑, In parallel, it increases the expressions of cytoprotective antioxidant proteins, such as heme oxygenase 1 (HO-1), peroxiredoxin (PRX), and thioredoxin (TRX), in macrophages [74].
*Prx↑,
*Trx↑,
*NRF2↑, inhibits reactive oxygen species by Kelch-like ECH-associated protein 1 (Keap-1)/nuclear factor erythroid-2-related factor (Nrf2)/heme oxygenase-1 (HO-1) pathway
*GSH↑, enhanced liver antioxidant capacities via glutathione (GSH), Trolox equivalent antioxidant capacity (TEAC), superoxide dismutase (SOD), and catalase (CAT), decreased lipid peroxidation and malondialdehyde (MDA) levels [
*SOD↑,
*Catalase↑,
*lipid-P↓,
*MDA↓,
*eff↝, Similar to free taurine [62,63,64], TUDCA has proven neuroprotective properties which were researched in the models of Alzheimer’s disease (AD)
*GutMicro↑, taurine has been associated with inhibited growth of harmful bacteria, including Proteobacteria and especially Helicobacter, and also increasing the production of SCFA in mouse feces [351] as well as the metabolism of taurine by microbiota
other↑, Similarly, taurine plays a protective role in acute ischemic stroke

1839-

VitK3,

Vitamin K3 derivative inhibits androgen receptor signaling in targeting aggressive prostate cancer cells

in-vitro,

Pca,

TumCP↓, VK3-OCH3 significantly inhibits the proliferation of both RC77-T and MDA-PCa-2b African American PCa cells and promotes apoptosis
Apoptosis↑,
TumCCA↑, blocking the cell cycle at G0
ROS↑, associated with the production of free radicals, such as intracellular and mitochondrial reactive oxygen species (ROS)
eff↓, antioxidants such as N-Acetylcysteine (NAC) and Glutathione (GSH) effectively negated the oxidative stress induced by VK3-OCH3 on PCa cell lines
AR↓, VK3-OCH3 reduces the expression of androgen receptor, TRX2, and anti-apoptotic signaling molecules such as Bcl-2 and TCTP
Trx↓,
Bcl-2↓,

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 29

Pathway results for Effect on Cancer / Diseased Cells:

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

antiOx↑, 2, Catalase↑, 4, GPx↑, 3, GSH↑, 8, GSH/GSSG↑, 1, GSR↑, 2, GSS↑, 1, GSTs↑, 1, HO-1↑, 3, Keap1↓, 1, ox-Keap1↑, 1, lipid-P↓, 3, MDA↓, 1, MDA↑, 1, NQO1↑, 3, NRF2↑, 10, NRF2⇅, 1, Prx↑, 2, ROS↓, 9, ROS↑, 1, ROS∅, 1, selenoP↑, 1, SOD↑, 3, SOD2↓, 1, Trx↓, 2, Trx↑, 10, TrxR↑, 1, TrxR1↑, 1,

Metal & Cofactor Biology ⓘ

IronCh↑, 2,

Mitochondria & Bioenergetics ⓘ

ATP↑, 2, MMP↑, 1, mtDam↓, 1,

Core Metabolism/Glycolysis ⓘ

ALAT↓, 1, G6PD↑, 1, GlucoseCon↓, 2, Glycolysis↝, 1, HK2↓, 2, lactateProd↓, 1, LDHA↓, 2, NADPH↓, 3, NADPH∅, 1, PFK2↓, 1, PFKFB2↓, 1, PKM2↓, 1, PONs↓, 1, PPARγ↑, 1, PPP↓, 1, SIRT1↑, 1, SIRT2↑, 1,

Cell Death ⓘ

Apoptosis↓, 1, Cyt‑c↑, 1, iNOS↓, 2, necrosis↓, 1,

Protein Folding & ER Stress ⓘ

HSP27↑, 1, HSP70/HSPA5↑, 1, HSPs↓, 1, HSPs↑, 2,

Proliferation, Differentiation & Cell State ⓘ

Diff↑, 1, neuroG↑, 1, TumCG↑, 1,

Migration ⓘ

TXNIP↑, 1,

Angiogenesis & Vasculature ⓘ

HIF2a↑, 1,

Barriers & Transport ⓘ

BBB↑, 1, GLUT4↑, 1,

Immune & Inflammatory Signaling ⓘ

CRP↓, 1, IFN-γ↓, 1, IL1↓, 1, IL6↓, 1, Inflam↓, 7, NF-kB↓, 1, TNF-α↓, 2,

Synaptic & Neurotransmission ⓘ

BDNF↑, 1, GABA↑, 1,

Drug Metabolism & Resistance ⓘ

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

Clinical Biomarkers ⓘ

ALAT↓, 1, CRP↓, 1, GutMicro↑, 2, IL6↓, 1,

Functional Outcomes ⓘ

AntiCan↑, 1, AntiDiabetic↑, 1, cognitive↑, 1, hepatoP↑, 2, memory↑, 1, neuroP↑, 1, radioP↑, 1,

Infection & Microbiome ⓘ

Bacteria↓, 1,
Total Targets: 90

Scientific Paper Hit Count for: Trx, Thioredoxin

4 Selenite (Sodium)
3 Piperlongumine
3 Parthenolide
3 Silymarin (Milk Thistle) silibinin
2 Curcumin
2 EGCG (Epigallocatechin Gallate)
2 Gambogic Acid
2 Radiotherapy/Radiation
2 Sulforaphane (mainly Broccoli)
1 Capsaicin
1 γ-linolenic acid (Borage Oil)
1 Honokiol
1 Magnetic Fields
1 Quercetin
1 Resveratrol
1 Rosmarinic acid
1 Selenium
1 Gemcitabine (Gemzar)
1 Taurine
1 VitK3,menadione

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

Database Query Results : , , Trx

Pathway results for Effect on Cancer / Diseased Cells:

Redox & Oxidative Stress ⓘ

Mitochondria & Bioenergetics ⓘ

Core Metabolism/Glycolysis ⓘ

Cell Death ⓘ

Transcription & Epigenetics ⓘ

Protein Folding & ER Stress ⓘ

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 ⓘ

Protein Folding & ER Stress ⓘ

Proliferation, Differentiation & Cell State ⓘ

Migration ⓘ

Angiogenesis & Vasculature ⓘ

Barriers & Transport ⓘ

Immune & Inflammatory Signaling ⓘ

Synaptic & Neurotransmission ⓘ

Drug Metabolism & Resistance ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

Infection & Microbiome ⓘ

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