Database Query Results : EGCG (Epigallocatechin Gallate), , β-catenin/ZEB1

EGCG, EGCG (Epigallocatechin Gallate): Click to Expand ⟱
Features:
EGCG (Epigallocatechin Gallate) is found in green tea. 100 times more effective than Vitamin C and 25 times more effective than Vitamin E at protecting cells from damage associated with oxidative stress.
EGCG Epigallocatechin Gallate (Green Tea) -Catechin
Summary:
1. Concentration is a factor that could determine whether green tea polyphenols act as antioxidants or pro-oxidants.
2. Poor bioavailability: taking EGCG capsules without food was better.
3. Cancer dosage 4g/day (2g twice per day)? with curcumin may help (another ref says 700–2100 mg/d)
4. EGCG is susceptible to oxidative degradation.
5. “As for the pH level, the acidic environments enhance the stability of EGCG”.
6. “EGCG may enhance nanoparticle uptake by tumor cells”
7. Might be iron chelator (removing iron from cancer cells)
8. Claimed as synergistic effect with chemotherapy ( cisplatin, bleomycin, gemcitabine.
9. May suppress glucose metabolism, interfere with VEGF, downregulate NF-κB and MMP-9, down-regulation of androgen-regulated miRNA-21.
10. Take with red pepper powder, Capsicum ratio 25:1 (based on half life, they did every 4 hr) (chili pepper vanilloid capsaicin).
11. EGCG mediated ROS formation can upregulate CTR1 expression via the ERK1/2/NEAT1 pathway, which can increase the intake of chemotherapeutic drugs such as cisplatin in NSCLC cells and act as a chemosensitizer [58]
12. Matcha green tea has highest EGCG (2-3X) because consuming leaf.
13. EGCG is an ENOX2 inhibitor.
14. Nrf2 activator in both cancer and normal cells. This example of lung cancer show both directions in different cell lines, but both toward optimim level.
Biological activity, EGCG has been reported to exhibit a range of effects, including:
    Antioxidant activity: 10-50 μM
     Anti-inflammatory activity: 20-50 μM
     Anticancer activity: 50-100 μM
     Cardiovascular health: 20-50 μM
     Neuroprotective activity: 10-50 μM

Drinking a cup (or two cups) of green tea (in which one might ingest roughly 50–100 mg of EGCG from brewed tea) generally results in peak plasma EGCG concentrations in the range of approximately 0.1 to 0.6 μM.

With higher, supplement-type doses (e.g., oral doses in the 500 mg–800 mg range that are sometimes studied for clinical benefits), peak plasma concentrations in humans can reach the low micromolar range, often reported around ~1–2 μM and in some cases up to 5 μM.

Reported values can range from about 25–50 mg of EGCG per gram of matcha powder.
In cases where the matcha is exceptionally catechin-rich, the content could reach 200–250 mg or more in 5 g.

-Peak plasma concentration roughly 1 to 2 hours after oral ingestion.
-Elimination half-life of EGCG in plasma is commonly reported to be in the range of about 3 to 5 hours.

Supplemental EGCG
Dose (mg)   ≈ Peak Plasma EGCG (µM)
~50 mg          ≈ 0.1–0.3 µM
~100 mg         ≈ 0.2–0.6 µM
~250 mg         ≈ 0.5–1.0 µM
~500 mg         ≈ 1–2 µM
~800 mg or higher  ≈ 1–5 µM

50mg of EGCG in 1g of matcha tea(1/2 teaspoon)

Studies on green tea extracts have employed doses roughly equivalent to 300–800 mg/day of EGCG. Excessive doses can cause liver toxicity in some cases.

Methods to improve bioavailability
-Lipid-based carriers or nanoemulsions
-Polymer-based nanoparticles or encapsulation
-Co-administration with ascorbic acid (vitamin C)
-Co-administration of adjuvants like piperine (perhaps sunflower lecithin and chitosan) -Using multiple smaller doses rather than one large single dose.
-Taking EGCG on an empty stomach or under fasting conditions, or aligning dosing with optimal pH conditions in the GI tract, may improve its absorption.(acidic environment is generally more favorable for its stability and absorption).
– EGCG is more stable under acidic conditions. In the stomach, where the pH is typically around 1.5 to 3.5, EGCG is less prone to degradation compared to the more neutral or basic environments of the small intestine.
- At neutral (around pH 7) or alkaline pH, EGCG undergoes auto-oxidation, reducing the effective concentration available for absorption.
– Although the stomach’s acidic pH helps maintain EGCG’s stability, most absorption occurs in the small intestine, where the pH is closer to neutral.
– To counterbalance the inherent instability in the intestine, strategies such as co-administration of pH-modifying agents (like vitamin C) are sometimes used. These agents help to maintain a slightly acidic environment in the gut microenvironment, potentially improving EGCG stability during its transit and absorption.
– The use of acidifiers or buffering agents in supplements may help preserve EGCG until it reaches the absorption sites.

-Note half-life 3–5 hours.
- low BioAv 1%? despite its limited absorption, it is rapidly disseminated throughout the body
Pathways:
- induce ROS production
- ROS↑ related: MMP↓(ΔΨm), ER Stress↑, UPR↑, GRP78↑, Ca+2↑, Cyt‑c↑, Caspases↑, DNA damage↑, cl-PARP↑, HSP↓, Prx,
- Does NOT Lower AntiOxidant defense in Cancer Cells: NRF2↑, TrxR↓**, SOD, GSH Catalase HO1 GPx
- 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↓, IGF-1↓, uPA↓, VEGF↓, FAK↓, RhoA↓, NF-κB↓, TGF-β↓, α-SMA↓, ERK↓
- reactivate genes thereby inhibiting cancer cell growth : HDAC↓, DNMTs↓, EZH2↓, P53↑, HSP↓, Sp proteins↓,
- cause Cell cycle arrest : TumCCA↑, cyclin D1↓, cyclin E↓, CDK2↓, CDK4↓, CDK6↓,
- inhibits Migration/Invasion : TumCMig↓, TumCI↓, TNF-α↓, FAK↓, ERK↓, EMT↓, TOP1↓,
- inhibits glycolysis /Warburg Effect and ATP depletion : HIF-1α↓, PKM2↓, cMyc↓, GLUT1↓, LDH↓, LDHA↓, HK2↓, PFKs↓, ECAR↓, OXPHOS↓, GRP78↑, Glucose↓, GlucoseCon↓
- inhibits angiogenesis↓ : VEGF↓, HIF-1α↓, Notch↓, FGF↓, PDGF↓, EGFR↓, Integrins↓,
- inhibits Cancer Stem Cells : CSC↓, Hh↓, GLi↓, GLi1↓, CD133↓, CD24↓, β-catenin↓, n-myc↓, Notch↓, OCT4↓,
- Others: PI3K↓, AKT↓, JAK↓, STAT↓, Wnt↓, β-catenin↓, AMPK, ERK↓, JNK, - SREBP (related to cholesterol).
- Synergies: chemo-sensitization, chemoProtective, RadioSensitizer, RadioProtective, Others(review target notes), Neuroprotective, Cognitive, Renoprotection, Hepatoprotective(possible damage at high dose), 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 / buffered Conditional Driver Biphasic redox modulation EGCG can act as a pro-oxidant in cancer cells (often metal-catalyzed) while functioning as an antioxidant in normal cells
2 Mitochondrial integrity / intrinsic apoptosis ↓ ΔΨm; ↑ caspase activation ↔ preserved Driver Execution of intrinsic apoptosis Mitochondrial stress and apoptosis follow ROS elevation in cancer cells
3 NF-κB signaling ↓ NF-κB activation ↓ inflammatory NF-κB tone Driver Suppression of survival and inflammatory transcription NF-κB inhibition explains chemosensitization and reduced survival signaling
4 PI3K → AKT → mTOR axis ↓ AKT / ↓ mTOR ↔ adaptive suppression Secondary Reduced growth and anabolic signaling AKT/mTOR inhibition contributes to growth suppression and stress responses
5 MAPK stress signaling (JNK / p38) ↑ JNK / ↑ p38 ↔ minimal Secondary Stress-activated apoptosis signaling MAPK activation often follows ROS increase and supports apoptotic signaling
6 Cell cycle regulation ↑ G1 or G2/M arrest ↔ largely spared Phenotypic Cytostatic growth control Cell-cycle arrest reflects upstream signaling disruption rather than direct CDK inhibition
7 HIF-1α / VEGF hypoxia–angiogenesis axis ↓ HIF-1α; ↓ VEGF ↔ minimal Secondary Anti-angiogenic pressure EGCG interferes with hypoxia-driven tumor adaptation
8 NRF2 antioxidant response ↑ NRF2 (adaptive, often insufficient) ↑ NRF2 (protective) Adaptive Stress compensation NRF2 reflects response to redox perturbation rather than a kill mechanism


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⟱
2992- EGCG,    Effects of Epigallocatechin-3-Gallate on Matrix Metalloproteinases in Terms of Its Anticancer Activity
- Review, Var, NA
AP-1↓, MMPs have binding sites for at least one transcription factor of AP-1, Sp1, and NF-κB, and EGCG can downregulate these transcription factors through signaling pathways mediated by reactive oxygen species
Sp1/3/4↓,
NF-kB↓,
ERK↓, EGCG can also decrease nuclear ERK, p38, heat shock protein-27 (Hsp27), and β-catenin levels, leading to suppression of MMPs’ expression.
P-gp↓,
HSP27↓,
β-catenin/ZEB1↓,
MMPs↓,
TNF-α↓, suppress the production of inflammatory cytokines such as TNFα and IL-1β.
IL1β↓,
MMP2↓, EGCG inhibited MMP2 secretion in glioblastoma cells.

3208- EGCG,    Induction of Endoplasmic Reticulum Stress Pathway by Green Tea Epigallocatechin-3-Gallate (EGCG) in Colorectal Cancer Cells: Activation of PERK/p-eIF2α/ATF4 and IRE1α
- in-vitro, Colon, HT29 - in-vitro, Nor, 3T3
TumCD↓, EGCG treatment was toxic to the HT-29 cell line
ER Stress↑, EGCG induced ER stress in HT-29 by upregulating immunoglobulin-binding (BiP), PKR-like endoplasmic reticulum kinase (PERK), phosphorylation of eukaryotic initiation factor 2 alpha subunit (eIF2α), activating transcription 4 (ATF4), and IRE1α
GRP78/BiP↑,
PERK↑,
eIF2α↑,
ATF4↑,
IRE1↑,
Apoptosis↑, Apoptosis was induced in HT-29 cells after the EGCG treatment, as shown by the Caspase 3/7 activity.
Casp3↑,
Casp7↑,
Wnt↓, (CRC) via suppression of the Wnt/β-catenin pathway
β-catenin/ZEB1↓,
*toxicity∅, This embryonic fibroblast cell line (3T3) has shown that the EGCG was not toxic to normal healthy cells, given the treatment at any concentration even at the highest concentration of EGCG (1000 μM).
UPR↑, ER stress is induced by EGCG and activates UPR proteins

3243- EGCG,    (−)-Epigallocatechin-3-Gallate Inhibits Colorectal Cancer Stem Cells by Suppressing Wnt/β-Catenin Pathway
CD133↓, used to determine the expression of CD133. We revealed that EGCG inhibited the spheroid formation capability of colorectal cancer cells as well as the expression of colorectal CSC markers, along with suppression of cell proliferation and induction o
CSCs↓,
TumCP↓,
Apoptosis↑,
Wnt↓, EGCG downregulated the activation of Wnt/β-catenin pathway,
β-catenin/ZEB1↓,

21- EGCG,    Tea polyphenols EGCG and TF restrict tongue and liver carcinogenesis simultaneously induced by N-nitrosodiethylamine in mice
- in-vivo, Liver, NA
HH↓, The up-regulation of self renewal Wnt/β-catenin, Hh/Gli1 pathways and their associated genes Cyclin D1, cMyc and EGFR along with down regulation of E-cadherin seen during the carcinogenesis processes were found to be modulated during the restriction
PTCH1↓,
Smo↓,
Gli1↓,
CD44↓, Both EGCG and TF significantly reduced (P b 0.05) CD44 positive cells in all the treated groups
β-catenin/ZEB1↓, GCG and TF could reduce β-catenin expression and its nu- clear activation in different cancers (

688- EGCG,  GEM,    Epigallocatechin-3-Gallate (EGCG) Suppresses Pancreatic Cancer Cell Growth, Invasion, and Migration partly through the Inhibition of Akt Pathway and Epithelial–Mesenchymal Transition: Enhanced Efficacy When Combined with Gemcitabine
- in-vitro, PC, NA
Zeb1↓,
β-catenin/ZEB1↓,
Vim↓,
Akt↓,
p‑IGFR↓,
TumCG↓,
TumCMig↓,
TumCI↓,

692- EGCG,    EGCG: The antioxidant powerhouse in lung cancer management and chemotherapy enhancement
- Review, NA, NA
ROS↑,
Apoptosis↑,
DNAdam↑,
CTR1↑,
JWA↑,
β-catenin/ZEB1↓, downregulation of the Wnt/β-catenin pathway interferes with CSC traits
P53↑,
Vim↓,
VEGF↓,
p‑Akt↓,
Hif1a↓,
COX2↓,
ERK↓,
NF-kB↓,
Akt↓,
Bcl-xL↓,
miR-210↓,

1012- EGCG,    Inhibition of beta-catenin/Tcf activity by white tea, green tea, and epigallocatechin-3-gallate (EGCG): minor contribution of H(2)O(2) at physiologically relevant EGCG concentrations
- in-vitro, Nor, HEK293
*H2O2↑,
*β-catenin/ZEB1↓,
*TCF-4↓,

4683- EGCG,    Epigallocatechin-3-gallate inhibits self-renewal ability of lung cancer stem-like cells through inhibition of CLOCK
- in-vitro, Lung, A549 - in-vitro, Lung, H1299 - in-vivo, Lung, A549
CSCs↓, it was demonstrated that EGCG suppressed the CSC-like characteristics of lung cancer cells by targeting CLOCK.
CD133↓, EGCG also decreased the ratio of CD133+ cells
CLOCK↓, The Wnt/β-catenin pathway was notably inactivated by the knockdown of CLOCK in A549 and H1299 sphere cells.
Wnt↓, Wnt/β-catenin signaling is blocked by the knockdown of CLOCK in lung CSCs
β-catenin/ZEB1↓,
CD44↓, EGCG decreased CD133, CD44, Sox2, Nanog, and Oct4 protein expression levels by targeting CLOCK
SOX2↓,
Nanog↓,
OCT4↓,

4682- EGCG,    Human cancer stem cells are a target for cancer prevention using (−)-epigallocatechin gallate
- Review, Var, NA
CSCs↓, EGCG inhibits the transcription and translation of genes encoding stemness markers, indicating that EGCG generally inhibits the self-renewal of CSCs.
EMT↓, EGCG inhibits the expression of the epithelial-mesenchymal transition phenotypes of human CSCs.
ChemoSen↑, Green tea prevents human cancer, and the combination of EGCG and anticancer drugs confers cancer treatment with tissue-agnostic efficacy.
CD133↓, CD133, CD44, ALDH1A1, Nanog, Oct4
CD44↓,
ALDH1A1↓,
Nanog↓,
OCT4↓,
TumCP↓, These results show that EGCG inhibits proliferation and induces apoptosis of lung CSCs
Apoptosis↑,
p‑GSK‐3β↓, EGCG (0–100 μM) inhibited the phosphorylation of glycogen synthase kinase 3β (GSK3β) at Ser 9, which significantly increases the expression of GSK3β, and decreases the expression of β-catenin and its downstream target gene c-Myc.
GSK‐3β↑,
β-catenin/ZEB1↓,
cMyc↓,
XIAP↓, EGCG (30–60 μM) inhibits the expression of X-linked inhibitor of apoptosis protein (XIAP), Bcl2, and survivin as well as that of the EMT markers vimentin, Slug, Snail, and nuclear β-catenin.
Bcl-2↓,
survivin↓,
Vim↓,
Slug↓,
Snail↓,

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↑, EGCG induces apoptosis by activating capase-3/7 and inhibiting the expression of Bcl-2, survivin and XIAP in CSCs.
Casp7↑,
Bcl-2↓,
survivin↓,
XIAP↓,
EMT↓, EGCG inhibits epithelial-mesenchymal transition by inhibiting the expression of vimentin, slug, snail and nuclear β-catenin, and the activity of LEF-1/TCF
Vim↓,
Slug↓,
Snail↓,
β-catenin/ZEB1↓,
LEF1↓, LEF1/TCF
TCF↓, LEF1/TCF
eff↑, inhibition of Nanog by shRNA enhanced the inhibitory effects of EGCG
CSCs↓, prostate cancer cell lines contain a small population of CD44+CD133+ cancer stem cells and their self-renewal capacity is inhibited by EGCG.
TumCG↓, EGCG inhibits the growth of cancer stem cells isolated from human prostate cancer cell lines
tumCV↓, EGCG inhibits the formation of primary and secondary tumor spheroids and cell viability of human prostate cancer stem cells

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↑, EGCG induces apoptosis by activating capase-3/7 and inhibiting the expression of Bcl-2, survivin and XIAP in CSCs.
Casp7↑,
Bcl-2↓,
survivin↓,
XIAP↓,
EMT↓,
Slug↓,
Snail↓,
β-catenin/ZEB1↓,
LEF1↓, LEF-1/TCF
CSCs↓, quercetin synergizes with EGCG in inhibiting the self-renewal properties of prostate CSCs, inducing apoptosis, and blocking CSC's migration and invasion.
Apoptosis↑,
TumCMig↓,
TumCI↓,
CD44↓, EGCG inhibits the self-renewal capacity of CD44+α2β1+CD133+ CSCs isolated from human primary prostate tumors,
CD133↓,


* 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 ⓘ

ROS↑, 1,  

Mitochondria & Bioenergetics ⓘ

XIAP↓, 3,  

Core Metabolism/Glycolysis ⓘ

cMyc↓, 1,  

Cell Death ⓘ

Akt↓, 2,   p‑Akt↓, 1,   Apoptosis↑, 5,   Bcl-2↓, 3,   Bcl-xL↓, 1,   Casp3↑, 3,   Casp7↑, 3,   JWA↑, 1,   survivin↓, 3,   TumCD↓, 1,  

Kinase & Signal Transduction ⓘ

Sp1/3/4↓, 1,  

Transcription & Epigenetics ⓘ

tumCV↓, 1,  

Protein Folding & ER Stress ⓘ

eIF2α↑, 1,   ER Stress↑, 1,   GRP78/BiP↑, 1,   HSP27↓, 1,   IRE1↑, 1,   PERK↑, 1,   UPR↑, 1,  

DNA Damage & Repair ⓘ

DNAdam↑, 1,   P53↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

ALDH1A1↓, 1,   CD133↓, 4,   CD44↓, 4,   CLOCK↓, 1,   CSCs↓, 5,   EMT↓, 3,   ERK↓, 2,   Gli1↓, 1,   GSK‐3β↑, 1,   p‑GSK‐3β↓, 1,   HH↓, 1,   p‑IGFR↓, 1,   Nanog↓, 2,   OCT4↓, 2,   PTCH1↓, 1,   Smo↓, 1,   SOX2↓, 1,   TCF↓, 1,   TumCG↓, 2,   Wnt↓, 3,  

Migration ⓘ

AP-1↓, 1,   LEF1↓, 2,   MMP2↓, 1,   MMPs↓, 1,   Slug↓, 3,   Snail↓, 3,   TumCI↓, 2,   TumCMig↓, 2,   TumCP↓, 2,   Vim↓, 4,   Zeb1↓, 1,   β-catenin/ZEB1↓, 10,  

Angiogenesis & Vasculature ⓘ

ATF4↑, 1,   Hif1a↓, 1,   miR-210↓, 1,   VEGF↓, 1,  

Barriers & Transport ⓘ

CTR1↑, 1,   P-gp↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 1,   IL1β↓, 1,   NF-kB↓, 2,   TNF-α↓, 1,  

Drug Metabolism & Resistance ⓘ

ChemoSen↑, 1,   eff↑, 1,  
Total Targets: 68

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

H2O2↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

TCF-4↓, 1,  

Migration ⓘ

β-catenin/ZEB1↓, 1,  

Functional Outcomes ⓘ

toxicity∅, 1,  
Total Targets: 4

Scientific Paper Hit Count for: β-catenin/ZEB1, β-catenin/ZEB1
11 EGCG (Epigallocatechin Gallate)
2 Quercetin
1 Gemcitabine (Gemzar)
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#:73  Target#:342  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

Home Page