Quercetin / β-catenin/ZEB1 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.
EMIQ bioavialability is about 3X that of Quercetin (Example Natural Factors brand)
Isoquercitrin is high bioaviability and efficiacy but at this time does not seem available as supplement.

-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


β-catenin/ZEB1, β-catenin/ZEB1: Click to Expand ⟱
Source: HalifaxProj (inactivate)
Type:
β-catenin and ZEB1 are two important proteins that play significant roles in cancer biology, particularly in the processes of cell adhesion, epithelial-mesenchymal transition (EMT), and tumor progression.
β-catenin is a key component of the Wnt signaling pathway, which is crucial for cell proliferation, differentiation, and survival. It also plays a role in cell-cell adhesion by linking cadherins to the actin cytoskeleton.
Role in Cancer: ZEB1 is often upregulated in cancer and is associated with increased invasiveness and metastasis. It can repress epithelial markers (like E-cadherin) and promote mesenchymal markers (like N-cadherin and vimentin), facilitating the transition to a more aggressive cancer phenotype.

(MMP)-2 and MMP-9, which are the down-stream targets of β-catenin and play a crucial role in cancer cell metastasis.
Scientific Papers found: Click to Expand⟱
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/PTGS2↓, 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/ABCB1↓, EGFR↓, GSK‐3β↓, mTOR↓, RAGE↓, HSP27↓, VEGF↓, TGF-β↓, COL1↓, COL3A1↓,
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↑,
60- QC,  EGCG,  isoFl,    The dietary bioflavonoid quercetin synergizes with epigallocathechin gallate (EGCG) to inhibit prostate cancer stem cell characteristics, invasion, migration and epithelial-mesenchymal transition
- in-vitro, Pca, pCSCs
Casp3↑, Casp7↑, Bcl-2↓, survivin↓, XIAP↓, EMT↓, Slug↓, Snail↓, β-catenin/ZEB1↓, LEF1↓, CSCs↓, Apoptosis↑, TumCMig↓, TumCI↓, CD44↓, CD133↓,
53- QC,    Quercetin regulates β-catenin signaling and reduces the migration of triple negative breast cancer
- in-vitro, BC, MDA-MB-231 - NA, NA, MDA-MB-468
E-cadherin↑, Vim↓, cycD1/CCND1↓, cMyc↓, EMT↓, TumCG↓, TumCMig↓, β-catenin/ZEB1↓, ChemoSen↑,
46- QC,    Quercetin, but Not Its Glycosidated Conjugate Rutin, Inhibits Azoxymethane-Induced Colorectal Carcinogenesis in F344 Rats
- in-vitro, Colon, F344
β-catenin/ZEB1↓, BioAv↓,
87- QC,    Quercetin inhibits prostate cancer by attenuating cell survival and inhibiting anti-apoptotic pathways
- in-vitro, Pca, LNCaP - in-vitro, Pca, DU145 - in-vitro, Pca, PC3
ROS⇅, BAX↑, PUMA⇅, β-catenin/ZEB1↓, Shc↓, TAp63α↑, MAPK↑, p‑p42↑, p‑p44↑, BIM↑,
85- QC,    Quercetin inhibits invasion, migration and signalling molecules involved in cell survival and proliferation of prostate cancer cell line (PC-3)
- in-vitro, Pca, PC3
uPA↓, uPAR↓, EGFR↓, NRAS↓, Jun↓, NF-kB↓, β-catenin/ZEB1↓, p38↑, MAPK↑, cJun↓, cFos↓, Raf↓, TumCI↓, TumCMig↓,
76- QC,    Multifaceted preventive effects of single agent quercetin on a human prostate adenocarcinoma cell line (PC-3): implications for nutritional transcriptomics and multi-target therapy
- in-vitro, Pca, PC3
aSmase↝, Diablo↑, Fas↓, Hsc70↓, Hif1a↓, Mcl-1↓, HSP90↓, FLT4↓, EphB4↓, DNA-PK↓, PARP1↓, ATM↓, XIAP↝, PLC↓, GnT-V↝, heparanase↝, NM23↑, CSR1↑, SPP1↓, DNMT1↓, HDAC4↓, CXCR4↓, β-catenin/ZEB1↓, FBXW7↝, AMACR↓, cycD1/CCND1↓, IGF-1R↓, IMPDH1↓, IMPDH2↓, HEC1↓, NHE1↓, NOS2↓,
77- QC,  EGCG,    The dietary bioflavonoid quercetin synergizes with epigallocathechin gallate (EGCG) to inhibit prostate cancer stem cell characteristics, invasion, migration and epithelial-mesenchymal transition
- in-vitro, Pca, CD44+ - in-vitro, NA, CD133+ - in-vitro, NA, PC3 - in-vitro, NA, LNCaP
Casp3↑, Casp7↑, Bcl-2↓, survivin↓, XIAP↓, EMT↓, Vim↓, Slug↓, Snail↓, β-catenin/ZEB1↓, LEF1↓, TCF↓, eff↑, CSCs↓, TumCG↓, tumCV↓,
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/KDR/Flk1↓, EMT↓, EGFR↓, MMP2↓, MMP↓, TumMeta↓, MMPs↓, Akt↓, Snail↓, N-cadherin↓, Vim↓, E-cadherin↑, STAT3↓, TGF-β↓, ROS↓, P53↑, BAX↑, PKCδ↓, PI3K↓, COX2/PTGS2↓, 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 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(tgid=1) ⓘ

GSH↓, 2,   HO-1↑, 1,   ROS↓, 1,   ROS↑, 3,   ROS⇅, 1,  

Mitochondria & Bioenergetics(tgid=3) ⓘ

MMP↓, 3,   p‑p42↑, 1,   Raf↓, 1,   XIAP↓, 3,   XIAP↝, 1,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

AMACR↓, 1,   cMyc↓, 3,  

Cell Death(tgid=5) ⓘ

Akt↓, 2,   p‑Akt↓, 1,   Apoptosis↑, 3,   ASK1↑, 1,   aSmase↝, 1,   BAX↑, 3,   Bcl-2↓, 3,   BIM↑, 1,   Casp10↑, 1,   Casp3↓, 1,   Casp3↑, 5,   Casp7↑, 2,   Casp8↑, 2,   Casp9↑, 3,   cFLIP↓, 2,   CSR1↑, 1,   Cyt‑c↑, 1,   Diablo↑, 2,   DR5↑, 2,   Fas↓, 1,   Fas↑, 1,   iNOS↓, 2,   MAPK↑, 2,   Mcl-1↓, 1,   p38↑, 2,   PUMA⇅, 1,   survivin↓, 3,   TNFR 1↑, 1,   TRAIL↑, 1,   TRAILR↑, 1,  

Kinase & Signal Transduction(tgid=6) ⓘ

AMPKα↑, 1,   Sp1/3/4↓, 1,  

Transcription & Epigenetics(tgid=7) ⓘ

cJun↓, 1,   ac‑H3↑, 1,   ac‑H4↑, 1,   other↓, 1,   Shc↓, 1,   SPP1↓, 1,   tumCV↓, 1,  

Protein Folding & ER Stress(tgid=8) ⓘ

ER Stress↑, 1,   Hsc70↓, 1,   HSP27↓, 1,   HSP90↓, 1,  

DNA Damage & Repair(tgid=10) ⓘ

ATM↓, 1,   DFF45↑, 1,   DNA-PK↓, 1,   DNMT1↓, 1,   DNMTs↓, 1,   P53↑, 2,   cl‑PARP↑, 1,   PARP1↓, 1,   PARP1↑, 1,   PCNA↓, 1,  

Cell Cycle & Senescence(tgid=11) ⓘ

cycD1/CCND1↓, 4,   TAp63α↑, 1,   TumCCA↑, 3,  

Proliferation, Differentiation & Cell State(tgid=12) ⓘ

CD133↓, 1,   CD44↓, 1,   cFos↓, 1,   CSCs↓, 3,   EMT↓, 5,   p‑ERK↓, 1,   FBXW7↝, 1,   GSK‐3β↓, 1,   HDAC↓, 1,   HDAC4↓, 1,   IGF-1R↓, 1,   Jun↓, 1,   mTOR↓, 1,   p‑mTOR↓, 1,   NOTCH1↓, 1,   NRAS↓, 1,   PI3K↓, 2,   PTEN↑, 1,   STAT3↓, 2,   TCF↓, 1,   TumCG↓, 2,  

Migration(tgid=13) ⓘ

AntiAg↓, 1,   Ca+2↑, 1,   Ca+2↝, 1,   CLDN2↓, 1,   COL1↓, 1,   COL3A1↓, 1,   CXCL12↓, 1,   E-cadherin↓, 1,   E-cadherin↑, 2,   EphB4↓, 1,   GnT-V↝, 1,   heparanase↝, 1,   Ki-67↓, 1,   LEF1↓, 3,   MMP2↓, 2,   MMP7↓, 1,   MMP9↓, 1,   MMPs↓, 2,   N-cadherin↓, 1,   NM23↑, 1,   p‑p44↑, 1,   PKCδ↓, 1,   RAGE↓, 1,   Slug↓, 3,   Snail↓, 4,   TGF-β↓, 2,   TSP-1↑, 2,   TumCI↓, 2,   TumCMig↓, 3,   TumMeta↓, 1,   uPA↓, 2,   uPAR↓, 1,   Vim↓, 4,   β-catenin/ZEB1↓, 10,  

Angiogenesis & Vasculature(tgid=14) ⓘ

angioG↓, 1,   EGFR↓, 3,   FLT4↓, 1,   Hif1a↓, 2,   NO↓, 1,   VEGF↓, 2,   VEGFR2/KDR/Flk1↓, 1,  

Barriers & Transport(tgid=15) ⓘ

NHE1↓, 1,   P-gp/ABCB1↓, 1,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

COX2/PTGS2↓, 2,   CXCR4↓, 2,   IFN-γ↓, 1,   IKKα↓, 1,   IL10↓, 1,   IL6↓, 2,   IL8↓, 1,   Inflam↓, 1,   NF-kB↓, 2,   TNF-α↓, 1,  

Cellular Microenvironment(tgid=17) ⓘ

PLC↓, 1,  

Hormonal & Nuclear Receptors(tgid=20) ⓘ

CDK6↓, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

BioAv↓, 1,   ChemoSen↑, 2,   eff↑, 5,   P450↓, 1,  

Clinical Biomarkers(tgid=22) ⓘ

EGFR↓, 3,   HEC1↓, 1,   IL6↓, 2,   Ki-67↓, 1,   NOS2↓, 1,   RAGE↓, 1,  

Functional Outcomes(tgid=23) ⓘ

IMPDH1↓, 1,   IMPDH2↓, 1,  
Total Targets: 156

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress(tgid=1) ⓘ

antiOx↑, 1,   NRF2↑, 1,   ROS↓, 1,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

Inflam↓, 1,  

Functional Outcomes(tgid=23) ⓘ

AntiCan↑, 1,  
Total Targets: 5

Scientific Paper Hit Count for: β-catenin/ZEB1, β-catenin/ZEB1
10 Quercetin
2 EGCG (Epigallocatechin Gallate)
1 isoflavones
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#:342  State#:%  Dir#:1
  wNotes=0  sortOrder:rid,rpid

 

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