EGCG (Epigallocatechin Gallate) / GLUT1 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


GLUT1, Glucose Transporter 1: Click to Expand ⟱
Source:
Type: protein
Also known as SLC2A1
An important hallmark in cancer cells is the increase in glucose uptake. GLUT1 is an important target in cancer treatment because cancer cells upregulate GLUT1, a membrane protein that facilitates the basal uptake of glucose in most cell types, to ensure the flux of sugar into metabolic pathways.
GLUT1 is a member of the facilitated glucose transporter family and is widely expressed in various tissues, including red blood cells, brain, and cancer cells.
GLUT1 has been shown to be overexpressed in many types of tumors, including breast, lung, and colon cancer. This overexpression may contribute to the development and progression of cancer by promoting glucose uptake and energy production in cancer cells.
GLUT1 is a protein that facilitates the transport of glucose across cell membranes. GLUT1 plays a role in the regulation of glucose metabolism in diabetes.
GLUT1 plays a role in the regulation of glucose metabolism in diabetes.
GLUT1 is also known to be involved in the Warburg effect.
GLUTs are expressed 10–12-fold higher in cancer cells than in healthy tissues, especially in highly proliferative and malignant tumors.

Downregulators:
-Resveratrol: associated with reduced GLUT1 expression.
-Curcumin: downregulate GLUT1 in various cancer cell lines
-Quercetin: downregulating the expression and function of GLUT1.
-EGCG: suppress GLUT1 expression
-Berberine: linked to decreased expression or activity of GLUT1.


Scientific Papers found: Click to Expand⟱
681- EGCG,    Suppressing glucose metabolism with epigallocatechin-3-gallate (EGCG) reduces breast cancer cell growth in preclinical models
- vitro+vivo, BC, NA
Casp3↑, Casp8↑, Casp9↑, TumAuto↑, Beclin-1↝, ATG5↝, GlucoseCon↓, lactateProd↓, ATP↝, HK2↓, LDHA↓, Hif1a↓, GLUT1↓, TumVol↓, VEGF↓,

Showing Research Papers: 1 to 1 of 1

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 1

Pathway results for Effect on Cancer / Diseased Cells:


Mitochondria & Bioenergetics

ATP↝, 1,  

Core Metabolism/Glycolysis

GlucoseCon↓, 1,   HK2↓, 1,   lactateProd↓, 1,   LDHA↓, 1,  

Cell Death

Casp3↑, 1,   Casp8↑, 1,   Casp9↑, 1,  

Autophagy & Lysosomes

ATG5↝, 1,   Beclin-1↝, 1,   TumAuto↑, 1,  

Angiogenesis & Vasculature

Hif1a↓, 1,   VEGF↓, 1,  

Barriers & Transport

GLUT1↓, 1,  

Functional Outcomes

TumVol↓, 1,  
Total Targets: 15

Pathway results for Effect on Normal Cells:


Total Targets: 0

Scientific Paper Hit Count for: GLUT1, Glucose Transporter 1
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#:566  State#:%  Dir#:1
wNotes=0 sortOrder:rid,rpid

 

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