Quercetin / GPx Cancer Research Results

QC, Quercetin: Click to Expand ⟱
Features:
Plant pigment (flavonoid) found in red wine, onions, green tea, apples and berries.
Quercetin is thought to contribute to anticancer effects through several mechanisms:
-Antioxidant Activity:
-Induction of Apoptosis:modify Bax:Bcl-2 ratio
-Anti-inflammatory Effects:
-Cell Cycle Arrest:
-Inhibition of Angiogenesis and Metastasis: (VEGF)

Cellular Pathways:
-PI3K/Akt/mTOR Pathway: central to cell proliferation, survival, and metabolism.
-MAPK/ERK Pathway: influencing cell proliferation, differentiation, and apoptosis.
-NF-κB Pathway: downregulate NF-κB
-JAK/STAT Pathway: interfere with the activation of STAT3
-Apoptotic Pathways: intrinsic (mitochondrial) and extrinsic (death receptor-mediated) pathways

Quercetin has been used at doses around 500–1000 mg per day
Quercetin’s bioavailability from foods or standard supplements can be low.

-Note half-life 11 to 28 hours.
BioAv low 1-10%, poor water-solubility, consuming with fat may improve bioavialability. also piperine or VitC.
Pathways:
- induce ROS production in cancer cells (higher dose). Typicallys Lowers ROS in normal cells(unless it is high dose?)or depends on Redox status?. "quercetin paradox"
- ROS↑ related: MMP↓(ΔΨm), ER Stress↑, UPR↑, GRP78↑, Ca+2↑, Cyt‑c↑, Caspases↑, DNA damage↑, cl-PARP↑, HSP↓, Prx,
- Confusing info about Lowering AntiOxidant defense in Cancer Cells: NRF2↓(some contrary), TrxR↓**, SOD↓(contrary), GSH↓ Catalase↓(contrary), HO1↓(some contrary), GPx">GPx↓(some contrary)
- Raises AntiOxidant defense in Normal Cells: ROS↓, NRF2↑, SOD↑, GSH↑, Catalase↑,
- lowers Inflammation : NF-kB↓, COX2↓, p38↓, Pro-Inflammatory Cytokines : NLRP3↓, IL-1β↓, TNF-α↓, IL-6↓, IL-8↓
- inhibit Growth/Metastases : TumMeta↓, TumCG↓, EMT↓, MMPs↓, MMP2↓, MMP9↓, TIMP2, IGF-1↓, uPA↓, VEGF↓, ROCK1↓, FAK↓, NF-κB↓, CXCR4↓, SDF1↓, TGF-β↓, α-SMA↓, ERK↓
- reactivate genes thereby inhibiting cancer cell growth : HDAC↓, DNMTs↓, EZH2↓, P53↑, HSP↓, Sp proteins↓, TET↑
- cause Cell cycle arrest : TumCCA↑, cyclin D1↓, cyclin E↓, CDK2↓, CDK4↓, CDK6↓,
- inhibits Migration/Invasion : TumCMig↓, TumCI↓, TNF-α↓, FAK↓, ERK↓, EMT↓, TOP1↓, TET1,
- inhibits glycolysis and ATP depletion : HIF-1α↓, PKM2↓, cMyc↓, GLUT1↓, LDH↓, LDHA↓, HK2↓, PFKs↓, PDKs↓, ECAR↓, OXPHOS↓, GRP78↑, GlucoseCon↓
- inhibits angiogenesis↓ : VEGF↓, HIF-1α↓, Notch↓, FGF↓, PDGF↓, EGFR↓,
- some indication of inhibiting Cancer Stem Cells : CSC↓, CK2↓, Hh↓, CD24↓, β-catenin↓, Notch2↓,
- Others: PI3K↓, AKT↓, JAK↓, STAT↓, Wnt↓, β-catenin↓, AMPK, α↓, ERK↓, JNK, - SREBP (related to cholesterol).
- Synergies: chemo-sensitization, chemoProtective, RadioSensitizer, RadioProtective, Others(review target notes), Neuroprotective, Cognitive, Renoprotection, Hepatoprotective, CardioProtective,

- Selectivity: Cancer Cells vs Normal Cells

Rank Pathway / Axis Cancer Cells Normal Cells Label Primary Interpretation Notes
1 Reactive oxygen species (ROS) ↑ ROS (dose-, metal-, context-dependent) ↓ ROS Conditional Driver Biphasic redox modulation Quercetin exhibits pro-oxidant behavior in cancer cells while protecting normal cells
2 Mitochondrial integrity / intrinsic apoptosis ↓ ΔΨm; ↑ caspase activation ↔ preserved Driver Execution of intrinsic apoptosis Mitochondrial dysfunction is a central apoptosis route in cancer cells
3 PI3K → AKT → mTOR axis ↓ AKT / ↓ mTOR ↔ adaptive suppression Driver Growth and survival inhibition AKT/mTOR suppression is a consistently reported upstream effect in cancer models
4 NF-κB signaling ↓ NF-κB activation ↓ inflammatory NF-κB tone Secondary Reduced survival and inflammatory transcription NF-κB inhibition contributes to chemosensitization and apoptosis susceptibility
5 MAPK signaling (JNK / p38) ↑ JNK / ↑ p38 ↔ minimal Secondary Stress-mediated apoptosis signaling MAPK activation supports apoptosis downstream of redox stress
6 Cell cycle regulation ↑ G1/S or G2/M arrest ↔ largely spared Phenotypic Cytostatic growth control Cell-cycle arrest reflects disruption of growth signaling
7 HIF-1α hypoxia signaling ↓ HIF-1α ↔ minimal Secondary Reduced hypoxia tolerance Quercetin interferes with hypoxia-driven transcriptional programs
8 NRF2 antioxidant response ↑ NRF2 (adaptive, context-dependent) ↑ NRF2 (protective) Adaptive Stress compensation NRF2 induction reflects redox buffering rather than primary cytotoxicity


GPx, Glutathione peroxidases: Click to Expand ⟱
Source:
Type:
Glutathione peroxidases (GPXs) are crucial antioxidant enzymes, counteracting reactive oxygen species (ROS).
Glutathione peroxidase (GPx) refers to a family of antioxidant enzymes that play a crucial role in protecting cells from oxidative stress by catalyzing the reduction of hydrogen peroxide and organic peroxides. There are several isoforms of GPx, including GPx1, GPx2, GPx3, and GPx4, each with distinct tissue distributions and functions.
GPX overexpression promotes proliferation and invasion in cancer cells. Glutathione peroxidase-1 (GPX1), the most abundant isoform, contributes to invasion, migration, cisplatin resistance, and proliferation in various cancers.

GPx expression is often elevated in various cancers and is generally associated with poorer prognosis due to its role in protecting cancer cells from oxidative stress and contributing to treatment resistance.


Scientific Papers found: Click to Expand⟱
2343- QC,    Pharmacological Activity of Quercetin: An Updated Review
- Review, Nor, NA
*ROS↓, *GSH↑, *Catalase↑, *SOD↑, *MDA↓, *GPx↑, *Copper↓, *Iron↓, Apoptosis↓, TumCCA↑, MMP2↓, MMP9↓, GlucoseCon↓, lactateProd↓, PKM2↓, GLUT1↓, LDHA↓, ROS↑,
39- QC,    A Comprehensive Analysis and Anti-Cancer Activities of Quercetin in ROS-Mediated Cancer and Cancer Stem Cells
- Analysis, NA, NA
ROS↑, GSH↓, IL6↓, COX2↓, IL8↓, iNOS↓, TNF-α↓, MAPK↑, ERK↑, SOD↑, ATP↓, Casp↑, PI3K/Akt↓, mTOR↓, NOTCH1↓, Bcl-2↓, BAX↑, IFN-γ↓, TumCP↓, TumCCA↑, Akt↓, P70S6K↓, *Keap1↓, *GPx↑, *Catalase↑, *HO-1↑, *NRF2↑, NRF2↑, eff↑, HIF-1↓,
79- QC,    Chemopreventive Effect of Quercetin in MNU and Testosterone Induced Prostate Cancer of Sprague-Dawley Rats
- in-vivo, Pca, NA
GSH↑, SOD↑, Catalase↑, GPx↑, GSR↑, IGF-1R↓, Akt↓, AR↓, TumCP↓, lipid-P↓, H2O2↓, Raf↓, p‑MEK↓, Bcl-2↑, Bcl-xL↑, Casp3↑, Casp8↑, Casp9↑,
3607- QC,    Mechanisms of Neuroprotection by Quercetin: Counteracting Oxidative Stress and More
- Review, AD, NA - Review, Park, NA
*neuroP↑, *NRF2↑, *PONs↑, *antiOx↑, *Inflam↓, *SIRT1↑, *eff↑, *ROS↓, *cognitive↑, *eff↑, *lipid-P↓, *GSH↑, *GPx↑, *SOD↑, *NRF2↑,
4296- QC,    A Flavonoid on the Brain: Quercetin as a Potential Therapeutic Agent in Central Nervous System Disorders
- Review, AD, NA
*Inflam↓, *COX2↓, *5LO↓, *antiOx↑, *BioAv↝, *GPx↑, *SOD↑, *Ach↑, *4-HNE↓, *CREB↑, *BDNF↑, *ROS↓, *GSH↑, *IL1β↓, *IL6↓, *TNF-α↓,
5025- QC,    New perspectives on the therapeutic potential of quercetin in non-communicable diseases: Targeting Nrf2 to counteract oxidative stress and inflammation
- Review, Nor, NA
*antiOx↑, *Inflam↓, *NRF2↓, *ROS↓, *cardioP↑, *HO-1↑, *Catalase↑, *GPx↑, *NQO1↑, *SIRT1↑,
3341- QC,    Antioxidant Activities of Quercetin and Its Complexes for Medicinal Application
- Review, Var, NA - Review, Stroke, NA
*antiOx↑, *BioAv↑, *GSH↑, *AChE↓, *BChE↓, *H2O2↓, *lipid-P↓, *SOD↑, *SOD2↑, *Catalase↑, *GPx↑, *neuroP↑, *HO-1↑, *cardioP↑, *MDA↓, *NF-kB↓, *IKKα↓, *ROS↓, *PI3K↑, *Akt↑, *hepatoP↑, P53↑, BAX↑, IGF-1R↓, Akt↓, AR↓, TumCP↓, GSH↑, SOD↑, Catalase↑, lipid-P↓, *TNF-α↓, *Ca+2↓,
114- VitC,  QC,    Chemoprevention of prostate cancer cells by vitamin C plus quercetin: role of Nrf2 in inducing oxidative stress
- in-vitro, Pca, PC3 - in-vitro, Pca, DU145
GPx↓, GSR↓, NQO1↓, NRF2↓, ROS↑,

Showing Research Papers: 1 to 8 of 8

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

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

Catalase↑, 2,   GPx↓, 1,   GPx↑, 1,   GSH↓, 1,   GSH↑, 2,   GSR↓, 1,   GSR↑, 1,   H2O2↓, 1,   lipid-P↓, 2,   NQO1↓, 1,   NRF2↓, 1,   NRF2↑, 1,   ROS↑, 3,   SOD↑, 3,  

Mitochondria & Bioenergetics ⓘ

ATP↓, 1,   p‑MEK↓, 1,   Raf↓, 1,  

Core Metabolism/Glycolysis ⓘ

GlucoseCon↓, 1,   lactateProd↓, 1,   LDHA↓, 1,   PI3K/Akt↓, 1,   PKM2↓, 1,  

Cell Death ⓘ

Akt↓, 3,   Apoptosis↓, 1,   BAX↑, 2,   Bcl-2↓, 1,   Bcl-2↑, 1,   Bcl-xL↑, 1,   Casp↑, 1,   Casp3↑, 1,   Casp8↑, 1,   Casp9↑, 1,   iNOS↓, 1,   MAPK↑, 1,  

DNA Damage & Repair ⓘ

P53↑, 1,  

Cell Cycle & Senescence ⓘ

TumCCA↑, 2,  

Proliferation, Differentiation & Cell State ⓘ

ERK↑, 1,   IGF-1R↓, 2,   mTOR↓, 1,   NOTCH1↓, 1,   P70S6K↓, 1,  

Migration ⓘ

MMP2↓, 1,   MMP9↓, 1,   TumCP↓, 3,  

Angiogenesis & Vasculature ⓘ

HIF-1↓, 1,  

Barriers & Transport ⓘ

GLUT1↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 1,   IFN-γ↓, 1,   IL6↓, 1,   IL8↓, 1,   TNF-α↓, 1,  

Hormonal & Nuclear Receptors ⓘ

AR↓, 2,  

Drug Metabolism & Resistance ⓘ

eff↑, 1,  

Clinical Biomarkers ⓘ

AR↓, 2,   IL6↓, 1,  
Total Targets: 55

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

4-HNE↓, 1,   antiOx↑, 4,   Catalase↑, 4,   Copper↓, 1,   GPx↑, 6,   GSH↑, 4,   H2O2↓, 1,   HO-1↑, 3,   Iron↓, 1,   Keap1↓, 1,   lipid-P↓, 2,   MDA↓, 2,   NQO1↑, 1,   NRF2↓, 1,   NRF2↑, 3,   ROS↓, 5,   SOD↑, 4,   SOD2↑, 1,  

Core Metabolism/Glycolysis ⓘ

CREB↑, 1,   PONs↑, 1,   SIRT1↑, 2,  

Cell Death ⓘ

Akt↑, 1,  

Transcription & Epigenetics ⓘ

Ach↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

PI3K↑, 1,  

Migration ⓘ

5LO↓, 1,   Ca+2↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 1,   IKKα↓, 1,   IL1β↓, 1,   IL6↓, 1,   Inflam↓, 3,   NF-kB↓, 1,   TNF-α↓, 2,  

Synaptic & Neurotransmission ⓘ

AChE↓, 1,   BChE↓, 1,   BDNF↑, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↑, 1,   BioAv↝, 1,   eff↑, 2,  

Clinical Biomarkers ⓘ

IL6↓, 1,  

Functional Outcomes ⓘ

cardioP↑, 2,   cognitive↑, 1,   hepatoP↑, 1,   neuroP↑, 2,  
Total Targets: 44

Scientific Paper Hit Count for: GPx, Glutathione peroxidases
8 Quercetin
1 Vitamin C (Ascorbic 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#:140  Target#:418  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

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