Quercetin / STAT3 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↓(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


STAT3, Signal transducer and activator of transcription 3: Click to Expand ⟱
Source:
Type: Oncogene
Stat3 (Signal Transducer and Activator of Transcription 3) is a transcription factor that plays a crucial role in various cellular processes, including cell growth, survival, differentiation, and immune response.
Stat3 is frequently found to be constitutively activated in many types of cancers, including breast, prostate, lung, and head and neck cancers. (associated with poor prognosis and reduced survival.)

-STAT3 is typically activated by cytokines (such as IL-6) and growth factors binding to their respective receptors.
-Activated STAT3 upregulates the expression of genes that promote cell cycle progression (e.g., cyclin D1) and anti-apoptotic proteins (e.g., Bcl-2, Bcl-xL).
Scientific Papers found: Click to Expand⟱
910- QC,    The Anti-Cancer Effect of Quercetin: Molecular Implications in Cancer Metabolism
tumCV↓, Apoptosis↑, PI3k/Akt/mTOR↓, Wnt/(β-catenin)↓, MAPK↝, ERK↝, TumCCA↑, H2O2↑, ROS↑, TumAuto↑, MMPs↓, P53↑, Casp3↑, Hif1a↓, cFLIP↓, IL6↓, IL10↓, lactateProd↓, Glycolysis↓, PKM2↓, GLUT1↓, COX2↓, VEGF↓, OCR↓, ECAR↓, STAT3↓, MMP2↓, MMP9:TIMP1↓, mTOR↓,
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↓,
916- QC,    Quercetin and cancer: new insights into its therapeutic effects on ovarian cancer cells
- Review, Ovarian, NA
COX2↓, CRP↓, ER Stress↑, Apoptosis↑, GRP78/BiP↑, CHOP↑, p‑STAT3↓, PI3K↓, Akt↓, mTOR↓, cMyc↓, cycD1/CCND1↓, cFLIP↓, IL6↓, IL10↓,
56- QC,    Quercetin inhibits epithelial–mesenchymal transition, decreases invasiveness and metastasis, and reverses IL-6 induced epithelial–mesenchymal transition, expression of MMP by inhibiting STAT3 signaling in pancreatic cancer cells
- in-vitro, PC, PANC1 - in-vitro, PC, PATU-8988
EMT↓, MMPs↓, MMP2↓, MMP7↓, STAT3↓, TumCI↓, TumMeta↓, tumCV↓,
95- QC,    Quercetin, a natural dietary flavonoid, acts as a chemopreventive agent
- in-vitro, Pca, PC3
p‑ERK↓, p‑STAT3↓, p‑Akt↓, N-cadherin↓, Vim↓, cycD1/CCND1↓, Snail↓, Slug↓, Twist↓, PCNA↓, EGFR↓, chemoPv↑,
82- QC,  ATG,    Arctigenin in combination with quercetin synergistically enhances the anti-proliferative effect in prostate cancer cells
- in-vitro, Pca, LNCaP
AR↓, PI3K/Akt↓, miR-21↓, STAT3↓, BAD↓, PRAS40↓, GSK‐3β↓, PSA↓, NKX3.1↑, Bax:Bcl2↑, miR-19b↓, miR-148a↓, AMPKα↓, TumCP↓, chemoPv↑, TumCMig↓,
3604- QC,    Quercetin enrich diet during the early-middle not middle-late stage of alzheimer’s disease ameliorates cognitive dysfunction
- in-vivo, AD, NA
*cognitive↑, *Aβ↓, *neuroP↑, *BACE↓, *p‑SMAD2↓, *p‑STAT3↓, *SPARC↓,
3380- QC,    Quercetin as a JAK–STAT inhibitor: a potential role in solid tumors and neurodegenerative diseases
- Review, Var, NA - Review, Park, NA - Review, AD, NA
JAK↓, STAT↓, Inflam↓, NO↓, COX2↓, CRP↓, selectivity↑, *neuroP↑, STAT3↓, cycD1/CCND1↓, MMP2↓, STAT4↓, JAK2↓, TumCP↓, Diff↓, *eff↑, *IL6↓, *TNF-α↓, *IL1β↓, *Aβ↓,
4686- QC,    Quercetin suppresses endometrial cancer stem cells via ERα-mediated inhibition of STAT3 signaling
- in-vitro, EC, EMN8 - in-vitro, EC, EMN21
CSCs↓, ALDH1A1↓, cMyc↓, Nanog↓, OCT4↓, STAT3↓, JAK2↓, STAT3↓, eff↑,
3354- QC,    Quercetin: Its Main Pharmacological Activity and Potential Application in Clinical Medicine
- Review, Var, NA
*ROS↓, *IronCh↓, *lipid-P↓, *GSH↑, *NRF2↑, TumCCA↑, ER Stress↑, P53↑, CDK2↓, cycA1/CCNA1↓, CycB/CCNB1↓, cycE/CCNE↓, cycD1/CCND1↓, PCNA↓, P21↑, p27↑, PI3K↓, Akt↓, mTOR↓, STAT3↓, cFLIP↓, cMyc↓, survivin↓, DR5↓, *Inflam↓, *IL6↓, *IL8↓, COX2↓, 5LO↓, *cardioP↑, *FASN↓, *AntiAg↑, *MDA↓,
3368- QC,    The potential anti-cancer effects of quercetin on blood, prostate and lung cancers: An update
- Review, Var, NA
*Inflam↓, *antiOx↑, *AntiCan↑, Casp3↓, p‑Akt↓, p‑mTOR↓, p‑ERK↓, β-catenin/ZEB1↓, Hif1a↓, AntiAg↓, VEGFR2↓, EMT↓, EGFR↓, MMP2↓, MMP↓, TumMeta↓, MMPs↓, Akt↓, Snail↓, N-cadherin↓, Vim↓, E-cadherin↑, STAT3↓, TGF-β↓, ROS↓, P53↑, BAX↑, PKCδ↓, PI3K↓, COX2↓, cFLIP↓, cycD1/CCND1↓, cMyc↓, IL6↓, IL10↓, Cyt‑c↑, TumCCA↑, DNMTs↓, HDAC↓, ac‑H3↑, ac‑H4↑, Diablo↑, Casp3↑, Casp9↑, PARP1↑, eff↑, PTEN↑, VEGF↓, NO↓, iNOS↓, ChemoSen↑, eff↑, eff↑, eff↑, uPA↓, CXCR4↓, CXCL12↓, CLDN2↓, CDK6↓, MMP9↓, TSP-1↑, Ki-67↓, PCNA↓, ROS↑, ER Stress↑,

Showing Research Papers: 1 to 11 of 11

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 11

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

GSH↓, 1,   H2O2↑, 1,   HO-1↑, 1,   ROS↓, 1,   ROS↑, 3,  

Mitochondria & Bioenergetics ⓘ

MMP↓, 2,   OCR↓, 1,   XIAP↓, 1,  

Core Metabolism/Glycolysis ⓘ

cMyc↓, 5,   ECAR↓, 1,   Glycolysis↓, 1,   lactateProd↓, 1,   PI3K/Akt↓, 1,   PI3k/Akt/mTOR↓, 1,   PKM2↓, 1,  

Cell Death ⓘ

Akt↓, 4,   p‑Akt↓, 2,   Apoptosis↑, 3,   BAD↓, 1,   BAX↑, 2,   Bax:Bcl2↑, 1,   Bcl-2↓, 1,   Casp10↑, 1,   Casp3↓, 1,   Casp3↑, 3,   Casp8↑, 1,   Casp9↑, 2,   cFLIP↓, 4,   Cyt‑c↑, 1,   Diablo↑, 1,   DR5↓, 1,   DR5↑, 1,   Fas↑, 1,   iNOS↓, 2,   MAPK↝, 1,   p27↑, 1,   survivin↓, 2,   TNFR 1↑, 1,   TRAILR↑, 1,  

Kinase & Signal Transduction ⓘ

AMPKα↓, 1,   Sp1/3/4↓, 1,  

Transcription & Epigenetics ⓘ

ac‑H3↑, 1,   ac‑H4↑, 1,   miR-21↓, 1,   other↓, 1,   tumCV↓, 2,  

Protein Folding & ER Stress ⓘ

CHOP↑, 1,   ER Stress↑, 3,   GRP78/BiP↑, 1,   HSP27↓, 1,  

Autophagy & Lysosomes ⓘ

TumAuto↑, 1,  

DNA Damage & Repair ⓘ

DFF45↑, 1,   DNMTs↓, 1,   NKX3.1↑, 1,   P53↑, 4,   cl‑PARP↑, 1,   PARP1↑, 1,   PCNA↓, 3,  

Cell Cycle & Senescence ⓘ

CDK2↓, 1,   cycA1/CCNA1↓, 1,   CycB/CCNB1↓, 1,   cycD1/CCND1↓, 6,   cycE/CCNE↓, 1,   P21↑, 1,   TumCCA↑, 4,  

Proliferation, Differentiation & Cell State ⓘ

ALDH1A1↓, 1,   CSCs↓, 2,   Diff↓, 1,   EMT↓, 3,   ERK↝, 1,   p‑ERK↓, 2,   GSK‐3β↓, 2,   HDAC↓, 1,   mTOR↓, 4,   p‑mTOR↓, 1,   Nanog↓, 1,   NOTCH1↓, 1,   OCT4↓, 1,   PI3K↓, 4,   PTEN↑, 1,   STAT↓, 1,   STAT3↓, 9,   p‑STAT3↓, 2,   STAT4↓, 1,   Wnt/(β-catenin)↓, 1,  

Migration ⓘ

5LO↓, 1,   AntiAg↓, 1,   Ca+2↝, 1,   CLDN2↓, 1,   COL1↓, 1,   COL3A1↓, 1,   CXCL12↓, 1,   E-cadherin↓, 1,   E-cadherin↑, 1,   Ki-67↓, 1,   LEF1↓, 1,   miR-148a↓, 1,   miR-19b↓, 1,   MMP2↓, 5,   MMP7↓, 2,   MMP9↓, 1,   MMP9:TIMP1↓, 1,   MMPs↓, 4,   N-cadherin↓, 2,   PKCδ↓, 1,   RAGE↓, 1,   Slug↓, 2,   Snail↓, 3,   TGF-β↓, 2,   TSP-1↑, 2,   TumCI↓, 1,   TumCMig↓, 1,   TumCP↓, 2,   TumMeta↓, 2,   Twist↓, 1,   uPA↓, 1,   Vim↓, 3,   β-catenin/ZEB1↓, 2,  

Angiogenesis & Vasculature ⓘ

angioG↓, 1,   EGFR↓, 3,   Hif1a↓, 2,   NO↓, 2,   VEGF↓, 3,   VEGFR2↓, 1,  

Barriers & Transport ⓘ

GLUT1↓, 1,   P-gp↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 6,   CRP↓, 2,   CXCR4↓, 1,   IFN-γ↓, 1,   IKKα↓, 1,   IL10↓, 3,   IL6↓, 4,   IL8↓, 1,   Inflam↓, 2,   JAK↓, 1,   JAK2↓, 2,   NF-kB↓, 1,   PSA↓, 1,   TNF-α↓, 1,  

Hormonal & Nuclear Receptors ⓘ

AR↓, 1,   CDK6↓, 1,  

Drug Metabolism & Resistance ⓘ

ChemoSen↑, 1,   eff↑, 5,   P450↓, 1,   selectivity↑, 1,  

Clinical Biomarkers ⓘ

AR↓, 1,   CRP↓, 2,   EGFR↓, 3,   IL6↓, 4,   Ki-67↓, 1,   PSA↓, 1,   RAGE↓, 1,  

Functional Outcomes ⓘ

chemoPv↑, 2,   PRAS40↓, 1,  
Total Targets: 155

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 1,   GSH↑, 1,   lipid-P↓, 1,   MDA↓, 1,   NRF2↑, 2,   ROS↓, 2,  

Metal & Cofactor Biology ⓘ

IronCh↓, 1,  

Core Metabolism/Glycolysis ⓘ

FASN↓, 1,  

Proliferation, Differentiation & Cell State ⓘ

p‑STAT3↓, 1,  

Migration ⓘ

AntiAg↑, 1,   p‑SMAD2↓, 1,   SPARC↓, 1,  

Immune & Inflammatory Signaling ⓘ

IL1β↓, 1,   IL6↓, 2,   IL8↓, 1,   Inflam↓, 2,   TNF-α↓, 1,  

Protein Aggregation ⓘ

Aβ↓, 2,   BACE↓, 1,  

Drug Metabolism & Resistance ⓘ

eff↑, 1,  

Clinical Biomarkers ⓘ

IL6↓, 2,  

Functional Outcomes ⓘ

AntiCan↑, 1,   cardioP↑, 1,   cognitive↑, 1,   neuroP↑, 2,  
Total Targets: 25

Scientific Paper Hit Count for: STAT3, Signal transducer and activator of transcription 3
11 Quercetin
1 Arctigenin
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#:373  State#:%  Dir#:1
  wNotes=0  sortOrder:rid,rpid

 

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