EGCG (Epigallocatechin Gallate) / H2O2 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


H2O2, Hydrogen peroxide (H2O2): Click to Expand ⟱
Source:
Type:
H2O2 is a reactive oxygen species (ROS) that can induce oxidative stress in cells. While low levels of ROS can promote cell signaling and proliferation, high levels can lead to DNA damage, apoptosis (programmed cell death), and other cellular dysfunctions. This dual role means that H2O2 can contribute to cancer development and progression, as oxidative stress can lead to mutations and genomic instability.
H2O2 can enhance the effectiveness of certain chemotherapeutic agents by increasing oxidative stress in cancer cells. Additionally, localized delivery of H2O2 has been explored as a means to selectively target and kill cancer cells while sparing normal cells.
Cancer cells often exhibit altered metabolism, leading to increased production of reactive oxygen species, including H2O2. This can result from enhanced mitochondrial activity, increased glycolysis, or other metabolic adaptations that are characteristic of cancer.


Reported H2O2 concentrations for representative compounds.
   Prooxidant          Dose                   Cell Line            H2O2 Produced
EGCG50 µMJurkat~1 µM
EGCG10 µMHCT116 and HT291.5 µM
EGCG100 µMJurkat20 µM
Quercetin70 µMHT292 µM
Menadione10 µMJurkat20 µM
Plumbagin4 µMSiHA and HeLa1 mM
β-Lap1 µMHL-6070 µM
Doxorubicin1 µMPC338 pM
Ascorbic Acid 1 mMHL-60161 µM
Ascorbic Acid0.2–2.0 mMLymphoma20–120 µM
Ascorbic Acidi.v. 0.5 mg/gRats0–20 µM
Ascorbic Acidi.p. 4.0 g/kgMice tumor> 125 µM
TiO210 µg/mLHepG2150 nmol/mL
Paclitaxel100 nMMCF7600 nM
Paclitaxel100 nMHL-601100 nM

Note: many products at lower concentrations act as antioxidants, instead of Prooxidants.

Generally, increased hydrogen peroxide and oxidative stress are associated with poor outcomes, while the specific context and cellular environment can modulate its effects.


Scientific Papers found: Click to Expand⟱
2309- EGCG,  Chemo,    Targeting Glycolysis with Epigallocatechin-3-Gallate Enhances the Efficacy of Chemotherapeutics in Pancreatic Cancer Cells and Xenografts
- in-vitro, PC, MIA PaCa-2 - in-vitro, Nor, HPNE - in-vitro, PC, PANC1 - in-vivo, NA, NA
TumCG↓, eff↑, ROS↑, ECAR↓, ChemoSen↑, selectivity↑, Glycolysis↓, PFK↓, PKA↓, HK2∅, LDHA∅, PFKP↓, PKM2↓, H2O2↑, TumW↓,
641- EGCG,  Se,    Antioxidant effects of green tea
ROS↑, H2O2↑, ROS⇅,
642- EGCG,    Prooxidant Effects of Epigallocatechin-3-Gallate in Health Benefits and Potential Adverse Effect
ROS↑, H2O2↑, Apoptosis↑, Trx↓, TrxR↓, JNK↑, HO-1↑, Fenton↑,
643- EGCG,    New insights into the mechanisms of polyphenols beyond antioxidant properties; lessons from the green tea polyphenol, epigallocatechin 3-gallate
- Analysis, NA, NA
H2O2↑, Fenton↑, PDGFR-BB↑, EGFR↓, VEGFR2↓, IGFR↓, Ca+2↑, NO↑, Sp1/3/4↓, NF-kB↓, AP-1↓, STAT1↓, STAT3↓, FOXO↓, mtDam↑, TumAuto↑,
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↓,
20- EGCG,    Potential Therapeutic Targets of Epigallocatechin Gallate (EGCG), the Most Abundant Catechin in Green Tea, and Its Role in the Therapy of Various Types of Cancer
- in-vivo, Liver, NA - in-vivo, Tong, NA
HH↓, Gli1↓, Smo↓, TNF-α↓, COX2↓, *antiOx↑, Hif1a↓, NF-kB↓, VEGF↓, STAT3↓, Bcl-2↓, P53↑, Akt↓, p‑Akt↓, p‑mTOR↓, EGFR↓, AP-1↓, BAX↑, ROS↑, Casp3↑, Apoptosis↑, NRF2↑, *H2O2↓, *NO↓, *SOD↑, *Catalase↑, *GPx↑, *ROS↓,
4874- Uro,  EGCG,    A Combination Therapy of Urolithin A+EGCG Has Stronger Protective Effects than Single Drug Urolithin A in a Humanized Amyloid Beta Knockin Mice for Late-Onset Alzheimer's Disease
- in-vivo, AD, NA
*motorD↑, *memory↑, *MitoP↑, *Aβ↓, *mitResp↑, *Nrf1↑, *PINK1↑, *PARK2↑, *ATG5↑, *Bcl-2↑, *H2O2↓, *ROS↓, *lipid-P↓, *mt-ATP↑,

Showing Research Papers: 1 to 7 of 7

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 7

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress

Fenton↑, 2,   H2O2↑, 4,   HO-1↑, 1,   NRF2↑, 1,   ROS↑, 4,   ROS⇅, 1,   Trx↓, 1,   TrxR↓, 1,  

Mitochondria & Bioenergetics

mtDam↑, 1,  

Core Metabolism/Glycolysis

ECAR↓, 1,   Glycolysis↓, 1,   HK2∅, 1,   LDHA∅, 1,   PFK↓, 1,   PFKP↓, 1,   PKM2↓, 1,  

Cell Death

Akt↓, 1,   p‑Akt↓, 1,   Apoptosis↑, 2,   BAX↑, 1,   Bcl-2↓, 1,   Casp3↑, 1,   JNK↑, 1,  

Kinase & Signal Transduction

Sp1/3/4↓, 1,  

Autophagy & Lysosomes

TumAuto↑, 1,  

DNA Damage & Repair

P53↑, 1,  

Proliferation, Differentiation & Cell State

FOXO↓, 1,   Gli1↓, 1,   HH↓, 1,   IGFR↓, 1,   p‑mTOR↓, 1,   Smo↓, 1,   STAT1↓, 1,   STAT3↓, 2,   TumCG↓, 1,  

Migration

AP-1↓, 2,   Ca+2↑, 1,   PKA↓, 1,  

Angiogenesis & Vasculature

EGFR↓, 2,   Hif1a↓, 1,   NO↑, 1,   PDGFR-BB↑, 1,   VEGF↓, 1,   VEGFR2↓, 1,  

Immune & Inflammatory Signaling

COX2↓, 1,   NF-kB↓, 2,   TNF-α↓, 1,  

Drug Metabolism & Resistance

ChemoSen↑, 1,   eff↑, 1,   selectivity↑, 1,  

Clinical Biomarkers

EGFR↓, 2,  

Functional Outcomes

TumW↓, 1,  
Total Targets: 52

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress

antiOx↑, 1,   Catalase↑, 1,   GPx↑, 1,   H2O2↓, 2,   H2O2↑, 1,   lipid-P↓, 1,   Nrf1↑, 1,   PARK2↑, 1,   ROS↓, 2,   SOD↑, 1,  

Mitochondria & Bioenergetics

mt-ATP↑, 1,   mitResp↑, 1,   PINK1↑, 1,  

Cell Death

Bcl-2↑, 1,  

Autophagy & Lysosomes

ATG5↑, 1,   MitoP↑, 1,  

Proliferation, Differentiation & Cell State

TCF-4↓, 1,  

Migration

β-catenin/ZEB1↓, 1,  

Angiogenesis & Vasculature

NO↓, 1,  

Protein Aggregation

Aβ↓, 1,  

Functional Outcomes

memory↑, 1,   motorD↑, 1,  
Total Targets: 22

Scientific Paper Hit Count for: H2O2, Hydrogen peroxide (H2O2)
7 EGCG (Epigallocatechin Gallate)
1 Chemotherapy
1 Selenium
1 Urolithin
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#:138  State#:%  Dir#:%
wNotes=0 sortOrder:rid,rpid

 

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