EGCG (Epigallocatechin Gallate) / CSCs Cancer Research Results

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


CSCs, Cancer Stem Cells: Click to Expand ⟱
Source:
Type:
Cancer Stem Cells

Phytochemicals (natural plant-derived compounds) that may affect CSCs:
Curcumin
— suppresses self-renewal and pathways (Wnt/Notch/Hedgehog).
Resveratrol
— shown to reduce CSC populations and sphere formation in multiple models.
Sulforaphane (from broccoli sprouts)
— reported to inhibit CSC properties and pathways; active in vitro and in vivo.
EGCG (epigallocatechin-3-gallate, green tea)
— reduces CSC markers and sphere formation in several cancer types.
Quercetin
— reported to inhibit CSC proliferation, self-renewal and invasiveness (breast, endometrial, others).
Berberine
— shown to suppress CSC “stemness” and reduce tumorigenic properties in multiple models.
Genistein (soy isoflavone)
— decreases CSC markers, sphere formation and stemness signaling in prostate/breast/other models.
Honokiol (Magnolia bark)
— shown to eliminate or suppress CSC-like populations in oral, colon, glioma models.
Luteolin
— inhibits stemness/EMT and reduces CSC markers and self-renewal in breast, prostate and other models.
Withaferin A (from Withania somnifera / ashwagandha)
— multiple preclinical reports show WA targets CSCs and reduces tumor growth/metastasis in models.

Circadian disruption in cancer and regulation of cancer stem cells by circadian clock genes: An updated review
Potential Role of the Circadian Clock in the Regulation of Cancer Stem Cells and Cancer Therapy
Can we utilise the circadian clock to target cancer stem cells?
Scientific Papers found: Click to Expand⟱
4656- CUR,  EGCG,    Curcumin and epigallocatechin gallate inhibit the cancer stem cell phenotype via down-regulation of STAT3-NFκB signaling
- in-vitro, BC, MDA-MB-231 - in-vitro, BC, MCF-7
CSCs↓, CD44↓, p‑STAT3↓, NF-kB↓, TumCI↓,
5397- CUR,  SFN,  RES,  EGCG,  Ash  Targeting Cancer Stem Cells with Phytochemicals: Molecular Mechanisms and Therapeutic Potential
- Review, Var, NA
CSCs↓,
3243- EGCG,    (−)-Epigallocatechin-3-Gallate Inhibits Colorectal Cancer Stem Cells by Suppressing Wnt/β-Catenin Pathway
CD133↓, CSCs↓, TumCP↓, Apoptosis↑, Wnt↓, β-catenin/ZEB1↓,
3244- EGCG,    Novel epigallocatechin gallate (EGCG) analogs activate AMP-activated protein kinase pathway and target cancer stem cells
AMPK↑, TumCP↓, P21↑, mTOR↓, CSCs↓, CD44↓, CD24↓,
22- EGCG,    Inhibition of sonic hedgehog pathway and pluripotency maintaining factors regulate human pancreatic cancer stem cell characteristics
- in-vitro, PC, CD133+ - in-vitro, PC, CD44+ - in-vitro, PC, CD24+ - in-vitro, PC, ESA+
HH↓, Smo↓, PTCH1↓, PTCH2↓, Gli1↓, GLI2↓, Gli↓, Bcl-2↓, XIAP↓, Shh↓, survivin↓, Casp3↑, Casp7↑, CSCs↓, Nanog↓, cMyc↓, OCT4↓, EMT↓, Snail↓, Slug↓, Zeb1↓, TumCMig↓, TumCI↓, eff↑,
678- EGCG,    Cancer Prevention with Green Tea and Its Principal Constituent, EGCG: from Early Investigations to Current Focus on Human Cancer Stem Cells
other↑, TumMeta↓, YMcells↑, CSCs↓,
679- EGCG,  5-FU,    Epigallocatechin-3-gallate targets cancer stem-like cells and enhances 5-fluorouracil chemosensitivity in colorectal cancer
- in-vitro, CRC, NA
NOTCH1↓, BMI1↓, SUZ12↓, EZH2↓, miR-34a↑, miR-200c↑, miR-145↑, CSCs↓,
4682- EGCG,    Human cancer stem cells are a target for cancer prevention using (−)-epigallocatechin gallate
- Review, Var, NA
CSCs↓, EMT↓, ChemoSen↑, CD133↓, CD44↓, ALDH1A1↓, Nanog↓, OCT4↓, TumCP↓, Apoptosis↑, p‑GSK‐3β↓, GSK‐3β↑, β-catenin/ZEB1↓, cMyc↓, XIAP↓, Bcl-2↓, survivin↓, Vim↓, Slug↓, Snail↓,
4685- EGCG,    Epigallocathechin gallate, polyphenol present in green tea, inhibits stem-like characteristics and epithelial-mesenchymal transition in nasopharyngeal cancer cell lines
- in-vitro, NPC, TW01 - in-vitro, NPC, TW06
CSCs↓, EMT↓, TumCMig↓, TumCI↓, OCT4↓, Snail↓, Vim↓, E-cadherin↓, HSP70/HSPA5↓, HSP90↓, AntiTum↓,
4684- EGCG,    EGCG inhibits CSC-like properties through targeting miR-485/CD44 axis in A549-cisplatin resistant cells
- in-vivo, NSCLC, A549
miR-485↑, CSCs↓, CD44↓,
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↓, CD133↓, CLOCK↓, Wnt↓, β-catenin/ZEB1↓, CD44↓, SOX2↓, Nanog↓, OCT4↓,
4680- EGCG,    The Potential of Epigallocatechin Gallate in Targeting Cancer Stem Cells: A Comprehensive Review
- Review, Var, NA
CSCs↓, EMT↓, TumMeta↓, RadioS↑, ChemoSen↑, BioAv↓,
4664- GEN,  CUR,  RES,  EGCG,  SFN  Targeting cancer stem cells by nutraceuticals for cancer therapy
- Review, Var, NA
CSCs↓, other↝, eff↑, CD44↓, p‑STAT3↓,
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↓,
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↓,

Showing Research Papers: 1 to 15 of 15

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 15

Pathway results for Effect on Cancer / Diseased Cells:


Mitochondria & Bioenergetics ⓘ

XIAP↓, 4,  

Core Metabolism/Glycolysis ⓘ

AMPK↑, 1,   cMyc↓, 2,  

Cell Death ⓘ

Apoptosis↑, 3,   Bcl-2↓, 4,   Casp3↑, 3,   Casp7↑, 3,   survivin↓, 4,  

Transcription & Epigenetics ⓘ

EZH2↓, 1,   miR-145↑, 1,   other↑, 1,   other↝, 1,   tumCV↓, 1,   YMcells↑, 1,  

Protein Folding & ER Stress ⓘ

HSP70/HSPA5↓, 1,   HSP90↓, 1,  

Cell Cycle & Senescence ⓘ

P21↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

ALDH1A1↓, 1,   BMI1↓, 1,   CD133↓, 4,   CD24↓, 1,   CD44↓, 7,   CLOCK↓, 1,   CSCs↓, 15,   EMT↓, 6,   Gli↓, 1,   Gli1↓, 1,   GSK‐3β↑, 1,   p‑GSK‐3β↓, 1,   HH↓, 1,   miR-34a↑, 1,   mTOR↓, 1,   Nanog↓, 3,   NOTCH1↓, 1,   OCT4↓, 4,   PTCH1↓, 1,   PTCH2↓, 1,   Shh↓, 1,   Smo↓, 1,   SOX2↓, 1,   p‑STAT3↓, 2,   SUZ12↓, 1,   TCF↓, 1,   TumCG↓, 1,   Wnt↓, 2,  

Migration ⓘ

E-cadherin↓, 1,   GLI2↓, 1,   LEF1↓, 2,   miR-200c↑, 1,   miR-485↑, 1,   Slug↓, 4,   Snail↓, 5,   TumCI↓, 4,   TumCMig↓, 3,   TumCP↓, 3,   TumMeta↓, 2,   Vim↓, 3,   Zeb1↓, 1,   β-catenin/ZEB1↓, 5,  

Immune & Inflammatory Signaling ⓘ

NF-kB↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 1,   ChemoSen↑, 2,   eff↑, 3,   RadioS↑, 1,  

Clinical Biomarkers ⓘ

EZH2↓, 1,   SUZ12↓, 1,  

Functional Outcomes ⓘ

AntiTum↓, 1,  
Total Targets: 67

Pathway results for Effect on Normal Cells:


Total Targets: 0

Scientific Paper Hit Count for: CSCs, Cancer Stem Cells
15 EGCG (Epigallocatechin Gallate)
3 Curcumin
2 Sulforaphane (mainly Broccoli)
2 Resveratrol
2 Quercetin
1 Ashwagandha(Withaferin A)
1 5-fluorouracil
1 Genistein (soy isoflavone)
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#:795  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

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