ARE Cancer Research Results

ARE, antioxidant responsive element (ARE): Click to Expand ⟱
Source:
Type:
antioxidant responsive element (ARE)
ARE in Normal Cells: Protective Role
ARE-regulated genes include NQO1, HO-1, GCLM, GCLC, and various glutathione S-transferases (GSTs).
-Detoxify reactive oxygen species (ROS)
-Agents like sulforaphane (from broccoli) can activate ARE in healthy cells to prevent cancer initiation.
-overactivation in cancer cells aids cancer survival, growth, resistance
Scientific Papers found: Click to Expand⟱
4265- CA,    Potential applications of nanomedicine for treating Parkinson's disease
- Review, Park, NA
*NRF2↑, Carnosic acid (CA) is defined as a natural product synthesized by plants of the Lamiaceae family, known for its potent Nrf2-ARE activating properties and neuroprotective role in early brain injury.
*ARE↑,
*neuroP↑,
*motorD↑, It enhances motor and cognitive function while modulating inflammatory markers in the central nervous system.
*cognitive↑,
*SOD↑, enhancement in the expression of superoxide dismutase, glutathione reductase, γ-glutamate-cysteine ligase modifier subunit, and γ-glutamate-cysteine ligase catalytic subunit, induction of caspase 3 cleavage
*GSR↑,
*NGF↑, Carnosic acid is a phenolic diterpene that promotes the synthesis of NGF in the glioblastoma cell lines and also enhances BDNF production in the dopaminergic neurons.
*BDNF↑,

5864- CA,    Carnosic acid, a catechol-type electrophilic compound, protects neurons both in vitro and in vivo through activation of the Keap1/Nrf2 pathway via S-alkylation of targeted cysteines on Keap1
- vitro+vivo, Stroke, PC12
*neuroP↑, neuroprotective effects of one such compound, carnosic acid (CA), found in the herb rosemary o
*GSH↑, CA translocates into the brain, increases the level of reduced glutathione in vivo, and protects the brain against middle cerebral artery ischemia/reperfusion,
*HO-1↑, Electrophiles induce the expression of a set of antioxidant enzymes, called ‘phase 2 enzymes,’ including heme oxygenase-1 (HO-1), NADPH quinone oxidoreductase 1 (NQO1
*NQO1↑,
*NRF2↑, arnosic acid activates the Keap1/Nrf2/ARE pathway
*ARE↑,
*ROS↓, These results suggest that CA protects primary CNS neurons against oxidative stress.
*BBB↑, Within 1 h, CA reached significant levels in the brain, suggesting that CA was able to penetrate the blood–brain barrier.

4333- Cyste,    Cystamine protects from 3-nitropropionic acid lesioning via induction of nf-e2 related factor 2 mediated transcription
- vitro+vivo, AD, NA
*NRF2↑, We found that cystamine activates Nrf2/ARE both in cell culture and in brain tissue and then probed the mechanism of activation in cell culture.
*ARE↑,
*neuroP↑, findings provide strong evidence that Nrf2 signaling may be an effective target for prevention of neurodegeneration.
*BDNF↑, cystamine has been shown to increase levels of brain derived neurotrophic factor (BDNF) in the striatum of HD knock-in mice and in primate blood.
*GSH↑, One effect of cystamine in cell culture is to increase glutathione (GSH) levels

3714- FA,    Recent Advances in the Neuroprotective Properties of Ferulic Acid in Alzheimer's Disease: A Narrative Review
- Review, AD, NA
*antiOx↑, antioxidant, anti-inflammatory and antidiabetic, thus suggesting it could be exploited as a possible novel neuroprotective strategy.
*Inflam↓,
*neuroP↑, neuroprotective strategy against AD due to its promising antioxidant and anti-inflammatory properties.
*NF-kB↓, inhibition of the nuclear factor kappa-B (NF-κ B), a key mediator of proinflammatory cytokine signaling pathway, which promotes the synthesis of interleukin (IL)-1β, IL-6, and tumor necrosis factor alpha (TNF-α), leading to neuroinflammation
*NLRP3↓, also inhibited the NLR pyrin domain-containing protein 3 (NLRP3) inflammasome
*iNOS↓, A down-regulation by ferulic acid of proinflammatory molecules, such as nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), TNF-α, IL-1β, vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1),
*COX2↓,
*TNF-α↓,
*IL1β↓,
*VCAM-1↓,
*ICAM-1↓,
*p‑MAPK↓, Ferulic acid was also able to affect the mitogen activated protein kinases (MAPKs) pathway, by inhibiting the phosphorylation of MAPKs, including p38 and c-Jun N-terminal kinase (JNK)
*p38↓,
*JNK↓,
*IL6↓, reduction of proinflammatory cytokines (IL-1β, IL-6, TNF-α and IL-8) mRNA expression
*IL8↓,
*hepatoP↑, ferulic acid reduces the liver damage induced by acetaminophen
*RenoP↑, renal protective effects by enhancing the CAT activity and PPAR γ gene expression
*Catalase↑,
*PPARγ↑,
*ROS↓, it was able to scavenge free radicals, inhibit the generation of reactive oxygen species (ROS)
*Fenton↓, inhibit the generation of reactive oxygen species (ROS) through the Fenton reaction, acting as a chelator of metals (i.e., Fe and Cu)
*IronCh↑,
*SOD↑, increasing the activity of the antioxidant superoxide dismutase (SOD) and catalase (CAT) enzymes
*MDA↓, lowering in the levels of malondialdehyde (MDA), a lipid peroxidation marker,
*lipid-P↓,
*NRF2↑, ferulic acid has been found associated to the modulation of several signaling pathways, and to an increased expression of the nuclear translocation of the transcription factor NF-E2-related factor (Nrf2)
*HO-1↑, Particularly, Nrf2 binds the antioxidant responsive element (ARE) in the promoter region of the heme oxygenase-1 (HO-1) gene,
*ARE↑,
*Bil↑, production of bilirubin, which acts as an efficient ROS scavenger, in human umbilical vein endothelial cells (HUVEC) under radiation-induced oxidative stress
*radioP↑,
*GCLC↑, HO-1 upregulation, an increased expression of other antioxidant genes, such as glutamate-cysteine ligase catalytic subunit (GCLC), glutamate-cysteine ligase regulatory subunit (GCLM), and NADPH quinone oxidoreductase-1 (NQO1) were induced by ferulic
*GCLM↑,
*NQO1↑,
*Half-Life↝, highest plasma concentration varies greatly depending on the investigated species: it is reached at 24 min and 2 min after ingestion in humans and rats, respectively
*GutMicro↑, ferulic acid esterified forms have been shown to act as a prebiotic, since they stimulate the growth of eubacteria, such as Lactobacilli and Bifidobacteria, in the human gastrointestinal tract, so preserving the homeostasis of gut microbiota,
*Aβ↓, ferulic acid was able to inhibit the aggregation of Aβ25–35, Aβ1–40, and Aβ1–42 and to destabilize pre-aggregated Aβ.
*BDNF↑, up-regulation of brain-derived neurotrophic factor (BDNF) gene were observed after treatment with ferulic acid
*Ca+2↓, prevented membrane damage, scavenged free radicals, increased SOD activity, and decreased the intracellular free Ca2+ levels, lipid peroxidation, and the release of prostaglandin E2 (PGE2);
*lipid-P↓,
*PGE2↓,
*cognitive↑, highlighted that ferulic administration (0.002–0.005% in drinking water) for 28 days improved the trimethyltin-induced cognitive deficit: an increase in the choline acetyltransferase activity was hypothesized as a possible mechanism of action.
*ChAT↑,
*memory↑, Another study showed that ferulic acid, administered intragastrically (30 mg/kg) for 3 months, improved memory in the transgenic APP/PS1 mice, and reduced Aβ deposits,
*Dose↝, 4-week prospective, open-label trial, in which patients (n = 20) assumed daily Feru-guard® (3.0 g/day), was designed.
*toxicity↓, Salau et al. [130] did not find signs of toxicity of ferulic acid in hippocampal neuronal cell lines HT22 cells, thus concluding that the substance seems to be safe in healthy brain cells

4801- Lyco,    Lycopene in the Prevention of Cardiovascular Diseases
- Review, CardioV, NA
*BioAv↝, Taking into account the fact that humans are not able to synthesize lycopene de novo, therefore its supply with food is necessary to take advantage of its pro-health properties.
*cardioP↑, protective effect on cardiovascular diseases
*BioAv↑, It is assumed that thanks to the cis form, lycopene is highly bioavailable in the human diet
*BioAv↑, bioavailability of lycopene as a result of its trans to cis isomerization can be achieved by adding fish oil or olive oil to tomato dishes.
*antiOx↑, Antioxidant Effects of Lycopene
*ROS↓, Lycopene is a highly effective antioxidant that, due to the high reactivity between the long polyene chain and free radicals, enables the elimination of singlet oxygen and the reduction of reactive oxygen species (ROS)
*ARE↑, activating the antioxidant response element (ARE)
*SOD↑, it increases the amount of antioxidant enzymes, which include superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px)
*Catalase↑,
*GPx↑,
*lipid-P↓, figure 3
*COX2↓, lycopene (in the form of watermelon powder) reduced inflammation by reducing the activity of the pro-inflammatory mediator cyclooxygenase 2 (COX-2),
*Inflam↓, Anti-Inflammatory Mechanism of Lycopene
*IL1β↓, inhibits the synthesis and release of pro-inflammatory cytokines, including IL-1β, IL-6, IL-8, and TNF-α.
*IL6↓,
*IL8↑,
*TNF-α↓,
*NF-kB↓, inhibition of the nuclear factor κB (NF-κB)
*BP↓, 15 or 30 mg of lycopene was associated with a significant reduction in systolic BP

4797- Lyco,    A mechanistic updated overview on lycopene as potential anticancer agent
- Review, Var, NA
AntiCan↑, The anticancer potential of lycopene has been described by various in vitro cells, animal studies, and some clinical trials.
antiOx↓, anticancer potential of lycopene is mainly due to its powerful singlet-oxygen quencher characteristics, simulation of detoxifying/antioxidant enzymes production,
Apoptosis↓, initiation of apoptosis, inhibition of cell proliferation and cell cycle progression as well as modulations of gap junctional communication, the growth factors, and signal transduction pathways
TumCP↓,
TumCCA↑,
Risk↓, The link between increased lycopene consumption and reducedoccurrence of a variety of cancers has been documented by in vitro cells,animal studies, and some clinical studies.
ROS↓, The antioxidant action of lycopene toward ROS
SOD↑, Lycopene can simulate detoxifying/antioxidant enzyme productionsuch as superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST), and glutathione reductase.
Catalase↑, . By stimulating ARE system, the lycopene can increase detoxifying/antioxidant enzymes production such as SOD, CAT, GST
GSTs↑,
ARE↑, The upregulating of the ARE system by lycopere has been studied in human BEAS-2B, HepG2, and MCF7
NRF2↑, figure 1
cycD1/CCND1↓, figure 2
cycE/CCNE↑,
CDK2↑,
p27↑,
BAX↑,
Bcl-2↓,
P53↑,
ChemoSen↑, Lycopene has also been declared to have a synergistic effect with drugs used in cancer treatment [16,17,27,32]. Lycopene may contribute to improved anticancer effects of enzalutamide


Showing Research Papers: 1 to 6 of 6

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 6

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

antiOx↓, 1,   ARE↑, 1,   Catalase↑, 1,   GSTs↑, 1,   NRF2↑, 1,   ROS↓, 1,   SOD↑, 1,  

Cell Death ⓘ

Apoptosis↓, 1,   BAX↑, 1,   Bcl-2↓, 1,   p27↑, 1,  

DNA Damage & Repair ⓘ

P53↑, 1,  

Cell Cycle & Senescence ⓘ

CDK2↑, 1,   cycD1/CCND1↓, 1,   cycE/CCNE↑, 1,   TumCCA↑, 1,  

Migration ⓘ

TumCP↓, 1,  

Drug Metabolism & Resistance ⓘ

ChemoSen↑, 1,  

Functional Outcomes ⓘ

AntiCan↑, 1,   Risk↓, 1,  
Total Targets: 20

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 2,   ARE↑, 5,   Bil↑, 1,   Catalase↑, 2,   Fenton↓, 1,   GCLC↑, 1,   GCLM↑, 1,   GPx↑, 1,   GSH↑, 2,   GSR↑, 1,   HO-1↑, 2,   lipid-P↓, 3,   MDA↓, 1,   NQO1↑, 2,   NRF2↑, 4,   ROS↓, 3,   SOD↑, 3,  

Metal & Cofactor Biology ⓘ

IronCh↑, 1,  

Core Metabolism/Glycolysis ⓘ

PPARγ↑, 1,  

Cell Death ⓘ

iNOS↓, 1,   JNK↓, 1,   p‑MAPK↓, 1,   p38↓, 1,  

Migration ⓘ

Ca+2↓, 1,   VCAM-1↓, 1,  

Barriers & Transport ⓘ

BBB↑, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 2,   ICAM-1↓, 1,   IL1β↓, 2,   IL6↓, 2,   IL8↓, 1,   IL8↑, 1,   Inflam↓, 2,   NF-kB↓, 2,   PGE2↓, 1,   TNF-α↓, 2,  

Synaptic & Neurotransmission ⓘ

BDNF↑, 3,   ChAT↑, 1,   NGF↑, 1,  

Protein Aggregation ⓘ

Aβ↓, 1,   NLRP3↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↑, 2,   BioAv↝, 1,   Dose↝, 1,   Half-Life↝, 1,  

Clinical Biomarkers ⓘ

Bil↑, 1,   BP↓, 1,   GutMicro↑, 1,   IL6↓, 2,  

Functional Outcomes ⓘ

cardioP↑, 1,   cognitive↑, 2,   hepatoP↑, 1,   memory↑, 1,   motorD↑, 1,   neuroP↑, 4,   radioP↑, 1,   RenoP↑, 1,   toxicity↓, 1,  
Total Targets: 58

Scientific Paper Hit Count for: ARE, antioxidant responsive element (ARE)
2 Carnosic acid
2 Lycopene
1 Cysteamine
1 Ferulic acid
Query results interpretion may depend on "conditions" listed in the research papers.
Such Conditions may include : 
  -low or high Dose
  -format for product, such as nano of lipid formations
  -different cell line effects
  -synergies with other products 
  -if effect was for normal or cancerous cells

Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:%  Target#:1354  State#:%  Dir#:2
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