Database Query Results : EGCG (Epigallocatechin Gallate), , TumCCA

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


TumCCA, Tumor cell cycle arrest: Click to Expand ⟱
Source:
Type:
Tumor cell cycle arrest refers to the process by which cancer cells stop progressing through the cell cycle, which is the series of phases that a cell goes through to divide and replicate. This arrest can occur at various checkpoints in the cell cycle, including the G1, S, G2, and M phases. S, G1, G2, and M are the four phases of mitosis.
Scientific Papers found: Click to Expand⟱
147- ATG,  EGCG,  CUR,    Increased chemopreventive effect by combining arctigenin, green tea polyphenol and curcumin in prostate and breast cancer cells
- in-vitro, Pca, LNCaP - in-vitro, Pca, MCF-7
Bax:Bcl2↑, combination treatment significantly increased the ratio of Bax to Bcl-2 proteins, decreased the activation of NFκB, PI3K/Akt and Stat3
NF-kB↓, arctigenin demonstrated the strongest ability to inhibit the activation of both PI3K/Akt and NFκB pathways in both LNCaP and MCF-7 cells.
PI3K/Akt↓,
STAT3↓,
chemoPv↑, combining Arc and EGCG with Cur to enhance chemoprevention in both prostate and breast cancer.
TumCP↓, combining Arc and EGCG with Cur to enhance chemoprevention in both prostate and breast cancer.
TumCCA↑, EGCG significantly increased the effect of curcumin on cell cycle arrest at G0/G1 phase in MCF-7 cells, and the effect was further enhanced by the addition of arctigenin
TumCMig↓, EGCG and arctigenin alone or in combination with curcumin significantly decreased the number of migrated MCF-7 cells compared to control

146- CUR,  EGCG,    Synergistic effect of curcumin on epigallocatechin gallate-induced anticancer action in PC3 prostate cancer cells
- in-vitro, Pca, PC3 - in-vitro, Pca, LNCaP - in-vitro, Pca, DU145
P21↑, The protein expressions of p21 were significantly increased by the co-treatment of EGCG and curcumin, whereas it was not changed by the treatment with each individual compound.
TumCCA↑, treatments of EGCG and curcumin arrested both S and G2/M phases of PC3 cells.
TumCP↓, EGCG inhibited PC3 cell proliferation to 11.2 and 24.3% at 50 and 100 μM, respectively.
BioAv↓, While curcumin has versatile anticancer properties, its poor absorption and low bioavailability are the challenges for its developmentas chemopreventive agent (33). The low bioavailability of EGCG is also confirmed i

3236- EGCG,  BA,    Molecular mechanisms for inhibition of colon cancer cells by combined epigenetic-modulating epigallocatechin gallate and sodium butyrate
- in-vitro, Colon, RKO - in-vitro, Colon, HCT116 - in-vitro, Colon, HT29
Apoptosis↑, combination treatment induced apoptosis and cell cycle arrest in RKO, HCT-116 and HT-29 colorectal cancer cells.
TumCCA?,
HDAC1↓, decrease in HDAC1, DNMT1, survivin and HDAC activity in all three cell lines.
DNMT1↓,
survivin↓,
HDAC↓,
P21↑, induction of p21 and an increase in nuclear factor kappa B (NF-κB)-p65.
NF-kB↑,
γH2AX↑, An increase in double strand breaks as determined by gamma-H2A histone family member X (γ-H2AX) protein levels
ac‑H3↑, induction of histone H3 hyperacetylation was also observed with combination treatment.
DNAdam↑,

3428- EGCG,    Thymoquinone Is a Multitarget Single Epidrug That Inhibits the UHRF1 Protein Complex
- Review, Var, NA
TumCCA↑, Our previous work revealed that epigallocatechin-3-gallate (EGCG) induced cell cycle arrest and apoptosis in Jurkat cells by the downregulation of UHRF1 and DNMT1, and the upregulation of the tumor suppressor p16
UHRF1↓,
DNMT1↓,
p16↑,

649- EGCG,  CUR,  PI,    Targeting Cancer Hallmarks with Epigallocatechin Gallate (EGCG): Mechanistic Basis and Therapeutic Targets
- Review, Var, NA
*BioEnh↑, increase EGCG bioavailability is using other natural products such as curcumin and piperine
EGFR↓,
HER2/EBBR2↓,
IGF-1↓,
MAPK↓,
ERK↓, reduction in ERK1/2 phosphorylation
RAS↓,
Raf↓, Raf-1
NF-kB↓, Numerous investigations have proven that EGCG has an inhibitory effect on NF-κB
p‑pRB↓, EGCG were displayed to reduce the phosphorylation of Rb, and as a result, cells were arrested in G1 phase
TumCCA↑, arrested in G1 phase
Glycolysis↓, EGCG has been found to inhibit key enzymes involved in glycolysis, such as hexokinase and pyruvate kinase, thereby disrupting the Warburg effect and inhibiting tumor cell growth
Warburg↓,
HK2↓,
Pyruv↓,

650- EGCG,    Cellular thiol status-dependent inhibition of tumor cell growth via modulation of retinoblastoma protein phosphorylation by (-)-epigallocatechin
- in-vitro, NA, NA
TumCCA↑, in the G1 phase
p‑pRB↓,

25- EGCG,  QC,    Quercetin Increased the Antiproliferative Activity of Green Tea Polyphenol (-)-Epigallocatechin Gallate in Prostate Cancer Cells
- in-vitro, Pca, PC3 - in-vitro, Pca, LNCaP
COMT↓, fact that EGCG primarily inhibited COMT activity, whereas quercetin reduced the amount of COMT protein.
TumCP↑, Quercetin and EGCG in combination synergistically inhibited cell proliferation, caused cell cycle arrest, and induced apoptosis in PC-3 cells.
TumCCA↑,
Apoptosis↑,

640- EGCG,    Epigallocatechin Gallate (EGCG) Is the Most Effective Cancer Chemopreventive Polyphenol in Green Tea
- in-vitro, CRC, HCT116 - in-vitro, Colon, SW480
TumCCA↑, induced cell cycle arrest in the G1 phase
Apoptosis↑,

989- EGCG,  Citrate,    In vitro and in vivo study of epigallocatechin-3-gallate-induced apoptosis in aerobic glycolytic hepatocellular carcinoma cells involving inhibition of phosphofructokinase activity
- in-vitro, HCC, NA - in-vivo, NA, NA
PFK↓,
Glycolysis↓, only inhibited glycolysis in cancer cells with a high rate of aerobic glycolysis (HCC-LM3 and HepG2 cells) but not in low-glycolytic cells (Huh-7 and LO2 cells).
lactateProd↓,
GlucoseCon↓,
TumCP↓,
TumCCA↑, arrests cells in S Phage
Casp3↑, citrate enhanced the EGCG upregulation of active caspase-3 and cleaved-PARP in both HCC-LM3 and HepG2 cells
cl‑PARP↑,
Apoptosis↑,
Casp8↑,
Casp9↑,
Cyt‑c↝, translocation of cytochrome c from the mitochondria into the cytosol
MMP↓,
BAD↑,
GLUT2↓, figure2 c,d
PKM2∅, figure2 c,d

668- EGCG,    The Potential Role of Epigallocatechin-3-Gallate (EGCG) in Breast Cancer Treatment
- Review, BC, MCF-7 - Review, BC, MDA-MB-231
HER2/EBBR2↓,
EGFR↓,
mtDam↑,
ROS↑,
PI3K/Akt↓,
P53↑,
P21↑,
Casp3↑,
Casp9↑,
BAX↑,
PTEN↑,
Bcl-2↓,
hTERT/TERT↓,
STAT3↓,
TumCCA↑, EGCG causes cell cycle arrest by preventing cyclin accumulation D1
Hif1a↓,

670- EGCG,    Epigallocatechin-3-gallate and its nanoformulation in cervical cancer therapy: the role of genes, MicroRNA and DNA methylation patterns
- Review, NA, NA
TumCCA↑, EGCG promoted G1 phase arrest
P53↑,
ERK↓, EGCG inactivated ERK1/2 protein kinases
EGFR↓,
p‑ERK↑,
VEGF↓,
Hif1a↓,
miR-203↓, in CA33 cells only
miR-210↑,

672- EGCG,    Molecular Targets of Epigallocatechin—Gallate (EGCG): A Special Focus on Signal Transduction and Cancer
- Review, NA, NA
DNMT1↓,
HDAC↓, HDAC1, HDAC2
G9a↓,
PRC2↓,
DNMT3A↓,
67LR↓, anti-proliferative action of EGCG is mediated by the binding to 67LR, whose expression is increased in tumour cells.
Apoptosis↑,
TumCCA↑,


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 12

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

ROS↑, 1,  

Mitochondria & Bioenergetics ⓘ

MMP↓, 1,   mtDam↑, 1,   Raf↓, 1,  

Core Metabolism/Glycolysis ⓘ

GlucoseCon↓, 1,   GLUT2↓, 1,   Glycolysis↓, 2,   HK2↓, 1,   lactateProd↓, 1,   PFK↓, 1,   PI3K/Akt↓, 2,   PKM2∅, 1,   Pyruv↓, 1,   Warburg↓, 1,  

Cell Death ⓘ

Apoptosis↑, 5,   BAD↑, 1,   BAX↑, 1,   Bax:Bcl2↑, 1,   Bcl-2↓, 1,   Casp3↑, 2,   Casp8↑, 1,   Casp9↑, 2,   Cyt‑c↝, 1,   hTERT/TERT↓, 1,   MAPK↓, 1,   survivin↓, 1,  

Kinase & Signal Transduction ⓘ

HER2/EBBR2↓, 2,  

Transcription & Epigenetics ⓘ

ac‑H3↑, 1,   p‑pRB↓, 2,   PRC2↓, 1,  

DNA Damage & Repair ⓘ

DNAdam↑, 1,   DNMT1↓, 3,   DNMT3A↓, 1,   G9a↓, 1,   p16↑, 1,   P53↑, 2,   cl‑PARP↑, 1,   UHRF1↓, 1,   γH2AX↑, 1,  

Cell Cycle & Senescence ⓘ

P21↑, 3,   TumCCA?, 1,   TumCCA↑, 11,  

Proliferation, Differentiation & Cell State ⓘ

ERK↓, 2,   p‑ERK↑, 1,   HDAC↓, 2,   HDAC1↓, 1,   IGF-1↓, 1,   PTEN↑, 1,   RAS↓, 1,   STAT3↓, 2,  

Migration ⓘ

67LR↓, 1,   miR-203↓, 1,   TumCMig↓, 1,   TumCP↓, 3,   TumCP↑, 1,  

Angiogenesis & Vasculature ⓘ

EGFR↓, 3,   Hif1a↓, 2,   miR-210↑, 1,   VEGF↓, 1,  

Immune & Inflammatory Signaling ⓘ

NF-kB↓, 2,   NF-kB↑, 1,  

Hormonal & Nuclear Receptors ⓘ

COMT↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 1,  

Clinical Biomarkers ⓘ

EGFR↓, 3,   HER2/EBBR2↓, 2,   hTERT/TERT↓, 1,  

Functional Outcomes ⓘ

chemoPv↑, 1,  
Total Targets: 67

Pathway results for Effect on Normal Cells:


Drug Metabolism & Resistance ⓘ

BioEnh↑, 1,  
Total Targets: 1

Scientific Paper Hit Count for: TumCCA, Tumor cell cycle arrest
12 EGCG (Epigallocatechin Gallate)
3 Curcumin
1 Arctigenin
1 Butyrate
1 Piperine
1 Quercetin
1 Citric Acid
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#:322  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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