Quercetin / GSH 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↓">GSH↓ Catalase↓(contrary), HO1↓(some contrary), GPx↓(some contrary)
- Raises AntiOxidant defense in Normal Cells: ROS↓, NRF2↑, SOD↑, GSH↑">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


GSH, Glutathione: Click to Expand ⟱
Source:
Type:
Glutathione (GSH) is a thiol antioxidant that scavenges reactive oxygen species (ROS), resulting in the formation of oxidized glutathione (GSSG). Decreased amounts of GSH and a decreased GSH/GSSG ratio in tissues are biomarkers of oxidative stress.
Glutathione is a powerful antioxidant found in every cell of the body, composed of three amino acids: cysteine, glutamine, and glycine. It plays a crucial role in protecting cells from oxidative stress, detoxifying harmful substances, and supporting the immune system.
cancer cells can have elevated levels of glutathione, which may help them survive in the oxidative environment created by the immune response and chemotherapy. This can make cancer cells more resistant to treatment.
While glutathione can be obtained from certain foods (like fruits, vegetables, and meats), its absorption from supplements is debated. Some people take N-acetylcysteine (NAC) or other precursors to boost glutathione levels, but the effects on cancer prevention or treatment are still being studied.
Depleting glutathione (GSH) to raise reactive oxygen species (ROS) is a strategy that has been explored in cancer research and therapy.
Many cancer cells have altered redox states and may rely on GSH to survive. Increasing ROS levels can induce stress in these cells, potentially leading to cell death.
Certain drugs and compounds can deplete GSH levels. For example, agents like buthionine sulfoximine (BSO) inhibit the synthesis of GSH, leading to its depletion.
Cancer cells tend to exhibit higher levels of intracellular GSH, possibly as an adaptive response to a higher metabolism and thus higher steady-state levels of reactive oxygen species (ROS).

"...intracellular glutathione (GSH) exhibits an astounding antioxidant activity in scavenging reactive oxygen species (ROS)..."
"Cancer cells have a high level of GSH compared to normal cells."
"...cancer cells are affluent with high antioxidant levels, especially with GSH, whose appearance at an elevated concentration of ∼10 mM (10 times less in normal cells) detoxifies the cancer cells." "Therefore, GSH depletion can be assumed to be the key strategy to amplify the oxidative stress in cancer cells, enhancing the destruction of cancer cells by fruitful cancer therapy."

The loss of GSH is broadly known to be directly related to the apoptosis progression.
Scientific Papers found: Click to Expand⟱
899- QC,    Intracellular metabolism and bioactivity of quercetin and its in vivo metabolites
- in-vivo, Var, NA
ROS↑, GSH↓,
1201- QC,    Quercetin: a silent retarder of fatty acid oxidation in breast cancer metastasis through steering of mitochondrial CPT1
- in-vivo, BC, NA
mitResp↓, Glycolysis↓, ATP↓, ROS↑, GSH↓, TumMeta↓, Apoptosis↑, FAO↓,
923- QC,    Quercetin as an innovative therapeutic tool for cancer chemoprevention: Molecular mechanisms and implications in human health
- Review, Var, NA
ROS↑, GSH↓, Ca+2↝, MMP↓, Casp3↑, Casp8↑, Casp9↑, other↓, *ROS↓, *NRF2↑, HO-1↑, TumCCA↑, Inflam↓, STAT3↓, DR5↑, P450↓, MMPs↓, IFN-γ↓, IL6↓, COX2↓, IL8↓, iNOS↓, TNF-α↓, cl‑PARP↑, Apoptosis↑, P53↑, Sp1/3/4↓, survivin↓, TRAILR↑, Casp10↑, DFF45↑, TNFR 1↑, Fas↑, NF-kB↓, IKKα↓, cycD1/CCND1↓, Bcl-2↓, BAX↑, PI3K↓, Akt↓, E-cadherin↓, Vim↓, β-catenin/ZEB1↓, cMyc↓, EMT↓, MMP2↓, NOTCH1↓, MMP7↓, angioG↓, TSP-1↑, CSCs↓, XIAP↓, Snail↓, Slug↓, LEF1↓, P-gp↓, EGFR↓, GSK‐3β↓, mTOR↓, RAGE↓, HSP27↓, VEGF↓, TGF-β↓, COL1↓, COL3A1↓,
921- QC,    Essential requirement of reduced glutathione (GSH) for the anti-oxidant effect of the flavonoid quercetin
- in-vitro, lymphoma, U937
ROS↑, GSH↓,
920- QC,    Interfering with ROS Metabolism in Cancer Cells: The Potential Role of Quercetin
- Review, NA, NA
GSH↓, ROS↑,
914- QC,    Quercetin and Cancer Chemoprevention
- Review, NA, NA
GSH↓, ROS↑, TumCCA↑, Ca+2↑, MMP↓, Casp3↑, Casp8↑, Casp9↑, β-catenin/ZEB1↓, AMPKα↑, ASK1↑, p38↑, TRAIL↑, DR5↑, cFLIP↓, Apoptosis↑,
35- QC,    Quercetin may act as a cytotoxic prooxidant after its metabolic activation to semiquinone and quinoidal product
- Study, NA, NA
ROS↑, GSH↓,
38- QC,    Quercetin inhibits prostate cancer by attenuating cell survival and inhibiting anti-apoptotic pathways
- in-vitro, Pca, DU145 - in-vitro, Pca, PC3
ROS⇅, GSH↓, PI3K/Akt⇅,
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↓,

Showing Research Papers: 1 to 9 of 9

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 9

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

GSH↓, 9,   HO-1↑, 1,   NRF2↑, 1,   ROS↑, 8,   ROS⇅, 1,   SOD↑, 1,  

Mitochondria & Bioenergetics ⓘ

ATP↓, 2,   mitResp↓, 1,   MMP↓, 2,   XIAP↓, 1,  

Core Metabolism/Glycolysis ⓘ

cMyc↓, 1,   FAO↓, 1,   Glycolysis↓, 1,   PI3K/Akt↓, 1,   PI3K/Akt⇅, 1,  

Cell Death ⓘ

Akt↓, 2,   Apoptosis↑, 3,   ASK1↑, 1,   BAX↑, 2,   Bcl-2↓, 2,   Casp↑, 1,   Casp10↑, 1,   Casp3↑, 2,   Casp8↑, 2,   Casp9↑, 2,   cFLIP↓, 1,   DR5↑, 2,   Fas↑, 1,   iNOS↓, 2,   MAPK↑, 1,   p38↑, 1,   survivin↓, 1,   TNFR 1↑, 1,   TRAIL↑, 1,   TRAILR↑, 1,  

Kinase & Signal Transduction ⓘ

AMPKα↑, 1,   Sp1/3/4↓, 1,  

Transcription & Epigenetics ⓘ

other↓, 1,  

Protein Folding & ER Stress ⓘ

HSP27↓, 1,  

DNA Damage & Repair ⓘ

DFF45↑, 1,   P53↑, 1,   cl‑PARP↑, 1,  

Cell Cycle & Senescence ⓘ

cycD1/CCND1↓, 1,   TumCCA↑, 3,  

Proliferation, Differentiation & Cell State ⓘ

CSCs↓, 1,   EMT↓, 1,   ERK↑, 1,   GSK‐3β↓, 1,   mTOR↓, 2,   NOTCH1↓, 2,   P70S6K↓, 1,   PI3K↓, 1,   STAT3↓, 1,  

Migration ⓘ

Ca+2↑, 1,   Ca+2↝, 1,   COL1↓, 1,   COL3A1↓, 1,   E-cadherin↓, 1,   LEF1↓, 1,   MMP2↓, 1,   MMP7↓, 1,   MMPs↓, 1,   RAGE↓, 1,   Slug↓, 1,   Snail↓, 1,   TGF-β↓, 1,   TSP-1↑, 1,   TumCP↓, 1,   TumMeta↓, 1,   Vim↓, 1,   β-catenin/ZEB1↓, 2,  

Angiogenesis & Vasculature ⓘ

angioG↓, 1,   EGFR↓, 1,   HIF-1↓, 1,   VEGF↓, 1,  

Barriers & Transport ⓘ

P-gp↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 2,   IFN-γ↓, 2,   IKKα↓, 1,   IL6↓, 2,   IL8↓, 2,   Inflam↓, 1,   NF-kB↓, 1,   TNF-α↓, 2,  

Drug Metabolism & Resistance ⓘ

eff↑, 1,   P450↓, 1,  

Clinical Biomarkers ⓘ

EGFR↓, 1,   IL6↓, 2,   RAGE↓, 1,  
Total Targets: 89

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

Catalase↑, 1,   GPx↑, 1,   HO-1↑, 1,   Keap1↓, 1,   NRF2↑, 2,   ROS↓, 1,  
Total Targets: 6

Scientific Paper Hit Count for: GSH, Glutathione
9 Quercetin
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#:137  State#:%  Dir#:1
  wNotes=0  sortOrder:rid,rpid

 

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