EGCG (Epigallocatechin Gallate) / selectivity 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

selectivity, selectivity: Click to Expand ⟱

Source:

Type:

The selectivity of cancer products (such as chemotherapeutic agents, targeted therapies, immunotherapies, and novel cancer drugs) refers to their ability to affect cancer cells preferentially over normal, healthy cells. High selectivity is important because it can lead to better patient outcomes by reducing side effects and minimizing damage to normal tissues.

Achieving high selectivity in cancer treatment is crucial for improving patient outcomes. It relies on pinpointing molecular differences between cancerous and normal cells, designing drugs or delivery systems that exploit these differences, and overcoming intrinsic challenges like tumor heterogeneity and resistance

Factors that affect selectivity:
1. Ability of Cancer cells to preferentially absorb a product/drug
-EPR-enhanced permeability and retention of cancer cells
-nanoparticle formations/carriers may target cancer cells over normal cells
-Liposomal formations. Also negatively/positively charged affects absorbtion

2. Product/drug effect may be different for normal vs cancer cells
- hypoxia
- transition metal content levels (iron/copper) change probability of fenton reaction.
- pH levels
- antiOxidant levels and defense levels

3. Bio-availability

Scientific Papers found: Click to Expand⟱

1503-

EGCG,

Epigenetic targets of bioactive dietary components for cancer prevention and therapy

Review,

NA,

IC50 values ranging from 0.21 to 0.47 μM

selectivity↑, DNMT1↓, RECK↑, MMPs↓, TumCI↓, angioG↓, TumMeta↓, HATs↓, IκB↑, NF-kB↓, IL6↓, COX2↓, NOS2↓, ac‑H3↑, ac‑H4↑, eff↑,

1514-

EGCG,

Preferential inhibition by (-)-epigallocatechin-3-gallate of the cell surface NADH oxidase and growth of transformed cells in culture

in-vitro,

Cerv,

HeLa

1-50uM

in-vitro,

Nor,

MCF10

selectivity↑, *toxicity∅, TumCG↓, NADHdeh?, eff↑, ENOX2↓, Dose?,

1515-

EGCG,

Phen,

Reciprocal Relationship Between Cytosolic NADH and ENOX2 Inhibition Triggers Sphingolipid-Induced Apoptosis in HeLa Cells

in-vitro,

Cerv,

HeLa

0.003 uM

in-vitro,

Nor,

MCF10

exceeded 20 uM

 note IC50 not reached for normal cells

in-vitro,

BC,

BT20

0.01 uM

selectivity↑, ENOX2↓, NADH↑, SK↓, eff↑, aSmase↑,

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

(20–100 μM) for 72 h

in-vitro,

Nor,

HPNE

in-vitro,

PC,

PANC1

in-vivo,

NA,

mice

TumCG↓, eff↑, ROS↑, ECAR↓, ChemoSen↑, selectivity↑, Glycolysis↓, PFK↓, PKA↓, HK2∅, LDHA∅, PFKP↓, PKM2↓, H2O2↑, TumW↓,

3238-

EGCG,

Green tea catechin, epigallocatechin-3-gallate (EGCG): mechanisms, perspectives and clinical applications

Review,

Var,

Telomerase↓, DNMTs↓, cycD1/CCND1↓, cycE/CCNE↓, CDK2↓, CDK4↓, CDK6↓, HATs↓, HDAC↓, selectivity↑, uPA↓, NF-kB↓, TNF-α↓, *ROS↓, *antiOx↑, Hif1a↓, VEGF↓, MMP2↓, MMP9↓, FAK↓, TIMP2↑, Mcl-1↓, survivin↓, XIAP↓, PCNA↓, p16↑, P21↑, p27↑, pRB↑, P53↑, MDM2↑, ROS↑, Casp3↑, Casp8↑, Casp9↑, Cyt‑c↑, Diablo↑, BAX⇅, cl‑PPARα↓, PDGF↓, EGFR↓, FOXO↑, AP-1↓, JNK↓, COX2↓, angioG↓,

3214-

EGCG,

EGCG-induced selective death of cancer cells through autophagy-dependent regulation of the p62-mediated antioxidant survival pathway

in-vitro,

Nor,

MRC-5

in-vitro,

Cerv,

HeLa

in-vitro,

Nor,

HEK293

in-vitro,

BC,

MDA-MB-231

in-vitro,

CRC,

HCT116

mTOR↓, AMPK↑, selectivity↑, ROS↑, selectivity↑, HO-1↓, *NRF2↑, NRF2↓, *HO-1↑,

Showing Research Papers: 1 to 6 of 6

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 6

Pathway results for Effect on Cancer / Diseased Cells:

Functional Outcomes ⓘ

TumW↓, 1,
Total Targets: 79

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

antiOx↑, 1, HO-1↑, 1, NRF2↑, 1, ROS↓, 1,

Functional Outcomes ⓘ

toxicity∅, 1,
Total Targets: 5

Scientific Paper Hit Count for: selectivity, selectivity

6 EGCG (Epigallocatechin Gallate)
1 PXD, phenoxodiol
1 Chemotherapy

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#:1110  State#:%  Dir#:2
  wNotes=0  sortOrder:rid,rpid

EGCG (Epigallocatechin Gallate) / selectivity Cancer Research Results

Pathway results for Effect on Cancer / Diseased Cells:

Redox & Oxidative Stress ⓘ

Mitochondria & Bioenergetics ⓘ

Core Metabolism/Glycolysis ⓘ

Cell Death ⓘ

Transcription & Epigenetics ⓘ

DNA Damage & Repair ⓘ

Cell Cycle & Senescence ⓘ

Proliferation, Differentiation & Cell State ⓘ

Migration ⓘ

Angiogenesis & Vasculature ⓘ

Immune & Inflammatory Signaling ⓘ

Hormonal & Nuclear Receptors ⓘ

Drug Metabolism & Resistance ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

Functional Outcomes ⓘ

Home Page