Nrf1 Cancer Research Results

Nrf1, Nuclear factor erythroid 2-related factor 1: Click to Expand ⟱
Source:
Type: transcription factor
Nrf1 (Nuclear factor erythroid 2-related factor 1) is a transcription factor that plays a crucial role in regulating cellular responses to stress, including oxidative stress and proteotoxic stress. While Nrf1 is generally considered a tumor suppressor, its expression and activity can be altered in various types of cancer, leading to either oncogenic or tumor-suppressive effects.

NRF1, together with related factors like NRF2, contributes to the cellular defense against oxidative damage by regulating antioxidant gene expression.

– This role can be double-edged: while it protects normal cells from damage, in cancer cells, enhanced antioxidant capacity might foster resistance to therapeutic agents that rely on oxidative stress to kill tumor cells.
Scientific Papers found: Click to Expand⟱
5344- Ajoene,    Ajoene, a Stable Garlic By-Product, Has an Antioxidant Effect through Nrf2-Mediated Glutamate-Cysteine Ligase Induction in HepG2 Cells and Primary Hepatocytes
- in-vitro, Nor, HepG2
*Nrf1↑, Ajoene treatment activated Nrf2, as indicated by increased phosphorylation and nuclear accumulation of Nrf2
*PKCδ↑, Ajoene activated protein kinase C-δ (PKCδ).
*GSH↑, Our results demonstrate that ajoene increases PKCd-dependent Nrf2 activation, GCL induction, and the cellular GSH concentration, which may contribute to protecting cells from oxidative stress.
*antiOx↑,

5871- CA,    Carnosic Acid Attenuates an Early Increase in ROS Levels during Adipocyte Differentiation by Suppressing Translation of Nox4 and Inducing Translation of Antioxidant Enzymes
- in-vitro, Nor, NA
*ROS↓, these results indicate that carnosic acid could down-regulate ROS level in an early stage of MPI-induced adipocyte differentiation
*NF-kB↓, attenuating ROS generation through suppression of NF-κB-mediated translation
*Nrf1↑, Carnosic Acid induces Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2)-Mediated Translation of Phase II Antioxidant Enzymes
*HO-1↑, HO-1 was significantly (p < 0.001) reduced by MDI hormone mixture compared to that of an undifferentiated treatment. However, it was enhanced by carnosic acid at 1–20 μM d
*GSTs↑, HO-1, γ-GCSc, and GST might be induced by carnosic acid, thus contributing to the down-regulation of ROS level

125- CUR,    Bioactivity of Curcumin on the Cytochrome P450 Enzymes of the Steroidogenic Pathway
- in-vitro, adrenal, H295R
CYP17A1↓,
CYP19↓,
*Nrf1↑, Curcumin has been shown to modulate molecular signaling pathways, such as the aryl hydrocarbon receptor, the induction of Nuclear factor erythroid 2-related factor 2 (Nrf2) or the inhibition of nuclear factor kappa-light-chain-enhancer of activated B
*NF-kB↓,
angioG↓, Curcumin can also inhibit angiogenesis and induce apoptosis on cancerous cells
Apoptosis↑,
AR↓, Curcumin has been shown to downregulate the androgen receptor in prostate cancer cells [11]
toxicity↓, Human trials using up to 8000 mg of curcumin found no evidence of toxicity [52].
BioAv↑, An important formulation has been the use of curcumin with piperine, which has been found to enhance the bioavailability as well as effects of curcumin

3231- EGCG,    Epigallocatechin-3-gallate restores mitochondrial homeostasis impairment by inhibiting HDAC1-mediated NRF1 histone deacetylation in cardiac hypertrophy
- in-vitro, Nor, NA
*HDAC↓, Administration of epigallocatechin-3-gallate (EGCG), an inhibitor of HDAC1, restored cardiac function, decreased heart/body weight and fibrosis
*cardioP↑,
*Nrf1↑, EGCG upregulated both NRF1 and PGC-1α in vitro
*PGC-1α↓,

4784- Lyco,    Protective effects of lycopene in cancer, cardiovascular, and neurodegenerative diseases: An update on epidemiological and mechanistic perspectives
- Review, Diabetic, NA - Review, CardioV, NA
*antiOx↑, Owing to its potent antioxidant properties, lycopene can potentially alleviate enhanced levels of proinflammatory mediators (e.g., proinflammatory cytokines IL-8, -6, and -1, and oxidized phospholipids) and prevent NF-κB activation
*IL8↓,
*IL6↓,
*IL1↓,
*NF-kB↓,
Inflam↓, graphical abstract
cycD1/CCND1↓,
MMP2↓,
MMP9↓,
Bcl-2↓,
NF-kB↓,
*Nrf1↑, normal cells
*antiOx↑,
*BDNF↑,
*neuroP↑,
*cardioP↑,
ROS↑, i) enhanced oxidative stress due to prooxidant activities of lycopene under circumstances of tumor cell
Dose↝, There are no known adverse effects from low (12 mg/day) to very high (150 mg/day) intake of dietary or formulated lycopene in a healthy population

4934- PEITC,    Differential induction of apoptosis in human breast cancer cell lines by phenethyl isothiocyanate, a glutathione depleting agent
- in-vitro, BC, MCF-7 - in-vitro, BC, MDA-MB-231
GSH↓, Phenethyl isothiocyanate (PEITC) is a naturally occurring electrophile which depletes intracellular glutathione (GSH) levels and triggers accumulation of reactive oxygen species (ROS)
ROS↑,
chemoPv↑, PEITC is of considerable interest as a potential chemopreventive/chemotherapeutic agent
Apoptosis↑, PEITC readily induced apoptosis in MDA-MB-231 cells (associated with rapid activation of caspases 9 and 3, and decreased expression of BAX), MCF7 cells were relatively resistant to the apoptosis promoting effects of PEITC.
Casp9↑,
Casp3↑,
eff↓, pre-treatment of MDA-MB-231 cells with NAC rendered these cells relatively resistant to PEITC-induced apoptosis.
TumCG↓, PEITC-induced growth inhibition in human breast cancer cell lines
TumCCA↑, There was also an increase in the proportion of cells in S phase, and cells with sub-G1 DNA content, indicative of cell death, especially after 48 h.
BAX↑, An increase in BAX expression was observed at 2 h after addition of PEITC in MDA-MB-231 cells, and BAX levels further increased at 4 and 6 h (
Nrf1↑, PEITC increased NRF2 expression by ~3-fold in MDA-MB-231 cells at 4 h after treatment with PEITC. By contrast, NRF2 expression in MCF7 cells was not effected by PEITC
GSH↓, Total GSH and GSSG levels were reduced in MCF7 cells at 2 h after treatment with PEITC, but then remained at this level for the remainder of the time course
GSSG↓,
GSH/GSSG↓, By contrast, in MDA-MB-231 cells, total GSH levels decreased up to 6 h and were reduced by ~50% at this time. There was also an increase in the GSSG/GSH ratio, indicative of increasing oxidative stress.

3343- QC,    Quercetin, a Flavonoid with Great Pharmacological Capacity
- Review, Var, NA - Review, AD, NA - Review, Arthritis, NA
*antiOx↑, Quercetin has a potent antioxidant capacity, being able to capture reactive oxygen species (ROS), reactive nitrogen species (RNS), and reactive chlorine species (ROC),which act as reducing agents by chelating transition-metal ions.
*ROS↓, Quercetin is a potent scavenger of reactive oxygen species (ROS), protecting the organism against oxidative stress
*angioG↓,
*Inflam↓, anti-inflammatory properties; the ability to protect low-density lipoprotein (LDL) oxidation, and the ability to inhibit angiogenesis;
*BioAv↓, It is known that the bioavailability of quercetin is usually relatively low (0.17–7 μg/mL), less than 10% of what is consumed, due to its poor water solubility (hydrophobicity), chemical stability, and absorption profile.
*Half-Life↑, their slow elimination since their half-life ranges from 11 to 48 h, which could favor their accumulation in plasma after repeated intakes
*GSH↑, Animal and cell studies have demonstrated that quercetin induces the synthesis of GSH
*SOD↑, increase in the expression of superoxide dismutase (SOD), catalase (CAT), and GSH with quercetin pretreatment
*Catalase↑,
*Nrf1↑, quercetin accomplishes this process involves increasing the activity of the nuclear factor erythroid 2-related factor 2 (NRF2), enhancing its binding to the ARE, reducing its degradation
*BP↓, quercetin has been shown to inhibit ACE activity, reducing blood pressure
*cardioP↑, quercetin has positive effects on cardiovascular diseases
*IL10↓, Under the influence of quercetin, the levels of interleukin 10 (IL-10), IL-1β, and TNF-α were reduced.
*TNF-α↓,
*Aβ↓, quercetin’s ability to modulate the enzyme activity in clearing amyloid-beta (Aβ) plaques, a hallmark of AD pathology.
*GSK‐3β↓, quercetin can inhibit the activity of glycogen synthase kinase 3β,
*tau↓, thus reducing tau aggregation and neurofibrillary tangles in the brain
*neuroP↑,
*Pain↓, quercetin reduces pain and inflammation associated with arthritis
*COX2↓, quercetin included the inhibition of oxidative stress, production of cytokines such as cyclooxygenase-2 (COX-2) and proteoglycan degradation, and activation of the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) (Nrf2/HO-1)
*NRF2↑,
*HO-1↑,
*IL1β↓, Mechanisms included decreased levels of TNF-α, IL-1β, IL-17, and monocyte chemoattractant protein-1 (MCP-1)
*IL17↓,
*MCP1↓,
PKCδ↓, studies with human leukemia 60 (HL-60) cells report that concentrations between 20 and 30 µM are sufficient to exert an inhibitory effect on cytosolic PKC activity and membrane tyrosine protein kinase (TPK) activity.
ERK↓, 50 µM resulted in the blockade of the extracellular signal-regulated kinases (ERK1/2) pathway
BAX↓, higher doses (75–100 µM) were used, as these doses reduced the expression of proapoptotic factors such as Bcl-2-associated X protein (Bax) and caspases 3 and 9
cMyc↓, induce apoptosis at concentrations of 80 µM and also causes a downregulation of cellular myelocytomatosis (c-myc) and Kirsten RAt sarcoma (K-ras) oncogenes
KRAS↓,
ROS↓, compound’s antioxidative effect changes entirely to a prooxidant effect at high concentrations, which induces selective cytotoxicity
selectivity↑, On the other hand, when noncancerous cells are exposed to quercetin, it exerts cytoprotective effects;
tumCV↓, decrease cell viability in human glioma cultures of the U-118 MG cell line as well as an increase in death by apoptosis and cell arrest at the G2 checkpoint of the cell cycle.
Apoptosis↑,
TumCCA↑,
eff↑, quercetin combined with doxorubicin can induce multinucleation of invasive tumor cells, downregulate P-glycoprotein (P-gp) expression, increase cell sensitivity to doxorubicin,
P-gp↓,
eff↑, resveratrol, quercetin, and catechin can effectively block the cell cycle and reduce cell proliferation in vivo
eff↑, cotreatment with epigallocatechin gallate (EGCG) inhibited catechol-O-methyltransferase (COMT) activity, decreasing COMT protein content and thereby arresting the cell cycle of PC-3 human prostate cancer cells
eff↑, synergistic treatment of tamoxifen and quercetin was also able to inhibit prostate tumor formation by regulating angiogenesis
eff↑, coadministration of 2.5 μM of EGCG, genistein, and quercetin suppressed the cell proliferation of a prostate cancer cell line (CWR22Rv1) by controlling androgen receptor and NAD (P)H: quinone oxidoreductase 1 (NQO1) expression
CycB/CCNB1↓, It can also downregulate cyclin B1 and cyclin-dependent kinase-1 (CDK-1),
CDK1↓,
CDK4↓, quercetin causes a decrease in cyclins D1/Cdk4 and E/Cdk2 and an increase in p21 in vascular smooth muscle cells
CDK2↓,
TOP2↓, quercetin is known to be a potent inhibitor of topoisomerase II (TopoII), a cell cycle-associated enzyme necessary for DNA replication
Cyt‑c↑, quercetin can induce apoptosis (cell death) through caspase-3 and caspase-9 activation, cytochrome c release, and poly ADP ribose polymerase (PARP) cleavage
cl‑PARP↑,
MMP↓, quercetin induces the loss of mitochondrial membrane potential, leading to the activation of the caspase cascade and cleavage of PARP.
HSP70/HSPA5↓, apoptotic effects of quercetin may result from the inhibition of HSP kinases, followed by the downregulation of HSP-70 and HSP-90 protein expression
HSP90↓,
MDM2↓, (MDM2), an onco-protein that promotes p53 destruction, can be inhibited by quercetin
RAS↓, quercetin can prevent Ras proteins from being expressed. In one study, quercetin was found to inhibit the expression of Harvey rat sarcoma (H-Ras), K-Ras, and neuroblastoma rat sarcoma (N-Ras) in human breast cancer cells,
eff↑, there was a substantial difference in EMT markers such as vimentin, N-cadherin, Snail, Slug, Twist, and E-cadherin protein expression in response to AuNPs-Qu-5, inhibiting the migration and invasion of MCF-7 and MDA-MB cells

3051- SK,    Resveratrol mediates its anti-cancer effects by Nrf2 signaling pathway activation
- Review, Var, NA
Nrf1↑, Resveratrol is a natural compound that can activate the Nrf2 transcription factor
Apoptosis↑, In different cell lines, resveratrol can increase apoptosis and inhibit the proliferation of cancer cells.
TumCP↓,
eff⇅, But there is a controversy on whether activation of Nrf2 is of clinical benefit in cancer therapy or is a carcinogen?
chemoP↑, chemoprevention effects
eff↑, It has also been suggested that reduction in oxidative conditions in cancer cells may enhance the anticancer effects of antineoplastic drugs [4].
VCAM-1↓, Resveratrol was effective on angiogenesis through an inhibitory direct effect on vascular endothelial growth factor (VEGF) generation and also inhibiting the hypoxia-inducible factor (HIF)-1generation and leads to preventing VEGF secretion
Hif1a↓,

4874- Uro,  EGCG,    A Combination Therapy of Urolithin A+EGCG Has Stronger Protective Effects than Single Drug Urolithin A in a Humanized Amyloid Beta Knockin Mice for Late-Onset Alzheimer's Disease
- in-vivo, AD, NA
*motorD↑, increased positive effects of urolithin A and a combination treatment of urolithin A+EGCG in hAbKI mice for phenotypic behavioral changes including motor coordination, locomotion/exploratory activity, spatial learning and working memory
*memory↑,
*MitoP↑, mitophagy and autophagy genes were upregulated
*Aβ↓, The levels of amyloid beta (Aβ) 40 and Aβ42 are reduced in both treatments, however, the reduction is higher for combined treatment
*mitResp↑, Mitochondrial respiration is stronger for urolithin A compared to EGCG, indicating that mitophagy enhancer, urolithin A is a better and more promising molecule to enhance mitophagy activity.
*Nrf1↑, table4
*PINK1↑,
*PARK2↑,
*ATG5↑,
*Bcl-2↑,
*H2O2↓, we found hydrogen peroxide levels were reduced in urolithin A (p = 0.0008) and urolithin A+EGCG (p = 0.0004) treated hAbKI mice relative to untreated mice.
*ROS↓, urolithin A and EGCG act as free radical scavengers in hAbKI mice
*lipid-P↓, (lipid peroxidation) were also significantly reduced in urolithin A (p = 0.0003) and urolithin A+EGCG (p = 0.0002) treated hAbKI mice relative to untreated hAbKI mice
*mt-ATP↑, mitochondrial ATP levels were increased in urolithin A (p = 0.007) and urolithin A+EGCG (p = 0.0002) treated hAbKI mice relative to hAbKI untreated mice.

4882- ZER,    An update of Nrf2 activators and inhibitors in cancer prevention/promotion
- Review, Var, NA
*Nrf1↑, There are many synthetic or extracted substances that function as Nrf2 activators (Fig. 3), which frequently are extracted from plants. Some examples of natural Nrf2 activators include curcumin, ... zerumbone


Showing Research Papers: 1 to 10 of 10

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 10

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

GSH↓, 2,   GSH/GSSG↓, 1,   GSSG↓, 1,   Nrf1↑, 2,   ROS↓, 1,   ROS↑, 2,  

Mitochondria & Bioenergetics ⓘ

MMP↓, 1,  

Core Metabolism/Glycolysis ⓘ

cMyc↓, 1,  

Cell Death ⓘ

Apoptosis↑, 4,   BAX↓, 1,   BAX↑, 1,   Bcl-2↓, 1,   Casp3↑, 1,   Casp9↑, 1,   Cyt‑c↑, 1,   MDM2↓, 1,  

Transcription & Epigenetics ⓘ

tumCV↓, 1,  

Protein Folding & ER Stress ⓘ

HSP70/HSPA5↓, 1,   HSP90↓, 1,  

DNA Damage & Repair ⓘ

cl‑PARP↑, 1,  

Cell Cycle & Senescence ⓘ

CDK1↓, 1,   CDK2↓, 1,   CDK4↓, 1,   CycB/CCNB1↓, 1,   cycD1/CCND1↓, 1,   TumCCA↑, 2,  

Proliferation, Differentiation & Cell State ⓘ

ERK↓, 1,   RAS↓, 1,   TOP2↓, 1,   TumCG↓, 1,  

Migration ⓘ

KRAS↓, 1,   MMP2↓, 1,   MMP9↓, 1,   PKCδ↓, 1,   TumCP↓, 1,   VCAM-1↓, 1,  

Angiogenesis & Vasculature ⓘ

angioG↓, 1,   Hif1a↓, 1,  

Barriers & Transport ⓘ

P-gp↓, 1,  

Immune & Inflammatory Signaling ⓘ

Inflam↓, 1,   NF-kB↓, 1,  

Hormonal & Nuclear Receptors ⓘ

AR↓, 1,   CYP19↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↑, 1,   CYP17A1↓, 1,   Dose↝, 1,   eff↓, 1,   eff↑, 7,   eff⇅, 1,   selectivity↑, 1,  

Clinical Biomarkers ⓘ

AR↓, 1,   KRAS↓, 1,  

Functional Outcomes ⓘ

chemoP↑, 1,   chemoPv↑, 1,   toxicity↓, 1,  
Total Targets: 55

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 4,   Catalase↑, 1,   GSH↑, 2,   GSTs↑, 1,   H2O2↓, 1,   HO-1↑, 2,   lipid-P↓, 1,   Nrf1↑, 8,   NRF2↑, 1,   PARK2↑, 1,   ROS↓, 3,   SOD↑, 1,  

Mitochondria & Bioenergetics ⓘ

mt-ATP↑, 1,   mitResp↑, 1,   PGC-1α↓, 1,   PINK1↑, 1,  

Cell Death ⓘ

Bcl-2↑, 1,  

Autophagy & Lysosomes ⓘ

ATG5↑, 1,   MitoP↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

GSK‐3β↓, 1,   HDAC↓, 1,  

Migration ⓘ

PKCδ↑, 1,  

Angiogenesis & Vasculature ⓘ

angioG↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 1,   IL1↓, 1,   IL10↓, 1,   IL17↓, 1,   IL1β↓, 1,   IL6↓, 1,   IL8↓, 1,   Inflam↓, 1,   MCP1↓, 1,   NF-kB↓, 3,   TNF-α↓, 1,  

Synaptic & Neurotransmission ⓘ

BDNF↑, 1,   tau↓, 1,  

Protein Aggregation ⓘ

Aβ↓, 2,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 1,   Half-Life↑, 1,  

Clinical Biomarkers ⓘ

BP↓, 1,   IL6↓, 1,  

Functional Outcomes ⓘ

cardioP↑, 3,   memory↑, 1,   motorD↑, 1,   neuroP↑, 2,   Pain↓, 1,  
Total Targets: 46

Scientific Paper Hit Count for: Nrf1, Nuclear factor erythroid 2-related factor 1
2 EGCG (Epigallocatechin Gallate)
1 Ajoene (compound of Garlic)
1 Carnosic acid
1 Curcumin
1 Lycopene
1 Phenethyl isothiocyanate
1 Quercetin
1 Shikonin
1 Urolithin
1 Zerumbone
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

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