EGCG (Epigallocatechin Gallate) / FIS1 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


FIS1, Mitochondrial fission 1 protein: Click to Expand ⟱
Source:
Type:

FIS1 — Mitochondrial fission 1 protein
FIS1 is a mitochondrial outer-membrane fission adaptor/receptor linked to DRP1-mediated mitochondrial dynamics. In cancer, FIS1 is an emerging target because mitochondrial fission supports proliferation, survival adaptation, metastatic behavior, and tumor-initiating/stem-like phenotypes in some models. Recent TNBC evidence suggests FIS1 is required for expansion of tumor-initiating cells and that FIS1 loss suppresses TIC activity without broadly collapsing mitochondrial function, making it a potentially more selective mitochondrial dynamics target than global DRP1 inhibition.

-Often pro-tumor, Supports mitochondrial fragmentation/dynamics in stress-adapted cells
Natural Product Reported FIS1 / Fission Effect Evidence Strength for FIS1 Cancer Relevance Database Classification Suggested Note
Curcumin Reported to decrease FIS1 and DRP1-associated mitochondrial fission in several mitochondrial injury models. Moderate to strong Indirect; FIS1-specific cancer evidence is limited. FIS1/DRP1 mitochondrial fission down-modulator Best-supported natural product to link with FIS1, but still mostly non-cancer evidence.
EGCG Reported to decrease FIS1 or regulate the DRP1/FIS1 mitochondrial dynamics axis in neuroprotection and injury models. Moderate Indirect; stronger evidence for mitochondrial quality control than cancer-specific FIS1 targeting. Possible FIS1 down-modulator Useful to tag under mitochondrial fission, mitophagy, and oxidative-stress adaptation.
Urolithin A Reported to decrease FIS1 and DRP1 while improving mitophagy and mitochondrial quality control. Moderate Indirect; mostly neurodegeneration/mitophagy evidence. FIS1/DRP1-associated mitochondrial quality-control modulator Better classified under mitophagy and mitochondrial quality control
Melatonin Often reported to reduce pathological DRP1/FIS1-mediated mitochondrial fission, but effects can be context-dependent. Moderate Indirect; cancer relevance is complex and context-dependent. Context-dependent mitochondrial dynamics modulator “normalizes mitochondrial dynamics” rather than simple FIS1 inhibition.
Resveratrol Can reduce pathological DRP1/FIS1 fission in some injury models, but may increase Fis1/Drp1 expression in aging-repair contexts. Mixed Indirect; direction may vary by model and dose. Context-dependent FIS1/DRP1 modulator not a simple FIS1 inhibitor; more a mitochondrial dynamics normalizer.
Quercetin Associated with FIS1 targeting in omics/computational studies; direct experimental FIS1 modulation is weaker. Weak to moderate Indirect; not validated as a FIS1-targeted anticancer compound. Putative FIS1-associated modulator Suitable as a low-confidence or “possible” FIS1 link.
Sulforaphane Inhibits mitochondrial fission mainly through DRP1-related mechanisms; direct FIS1 modulation is unclear. Weak for FIS1 specifically Indirect; relevant to cancer metabolism and oxidative stress, but not FIS1-specific. Broader DRP1/fission pathway modulator mitochondrial fission rather than direct FIS1 modulation.
Berberine Reported to inhibit DRP1-mediated mitochondrial fission; FIS1 is mainly implicated as part of the pathway rather than directly modulated. Weak for FIS1 specifically Indirect; potentially relevant to cancer metabolism but not validated through FIS1. Broader DRP1/fission pathway modulator not a direct FIS1 modulator unless using a broader mitochondrial fission category.


Scientific Papers found: Click to Expand⟱
6411- EGCG,    Pharmacological and Genetic Approaches to Downregulate FIS1 Mitigate Neuropathic Pain
- in-vivo, Nor, NA
*FIS1↓, *Pain↓, *ROS↓,
6410- EGCG,    Evaluation of the neuroprotective effect of EGCG: a potential mechanism of mitochondrial dysfunction and mitochondrial dynamics after subarachnoid hemorrhage
- in-vitro, Nor, NA
*FIS1↓, *neuroP↑, *Ca+2↓, *VGCC↝, *ROS↓, *DNAdam↓, *Apoptosis↓,
6412- 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
*Aβ↓, *eff↑, *cognitive↑, *neuroG↑, *BBB↑, *TNF-α↓, *IL1β↓, *IL6↓, *p‑tau↓, *FIS1↓, *ATP↑, *lipid-P↓,

Showing Research Papers: 1 to 3 of 3

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 3

Pathway results for Effect on Cancer / Diseased Cells:


Total Targets: 0

Pathway results for Effect on Normal Cells:


NA, unassigned

FIS1↓, 3,  

Redox & Oxidative Stress

lipid-P↓, 1,   ROS↓, 2,  

Mitochondria & Bioenergetics

ATP↑, 1,  

Cell Death

Apoptosis↓, 1,  

DNA Damage & Repair

DNAdam↓, 1,  

Proliferation, Differentiation & Cell State

neuroG↑, 1,   VGCC↝, 1,  

Migration

Ca+2↓, 1,  

Barriers & Transport

BBB↑, 1,  

Immune & Inflammatory Signaling

IL1β↓, 1,   IL6↓, 1,   TNF-α↓, 1,  

Synaptic & Neurotransmission

p‑tau↓, 1,  

Protein Aggregation

Aβ↓, 1,  

Drug Metabolism & Resistance

eff↑, 1,  

Clinical Biomarkers

IL6↓, 1,  

Functional Outcomes

cognitive↑, 1,   neuroP↑, 1,   Pain↓, 1,  
Total Targets: 20

Scientific Paper Hit Count for: FIS1, Mitochondrial fission 1 protein
3 EGCG (Epigallocatechin Gallate)
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#:1486  State#:%  Dir#:%
wNotes=0 sortOrder:rid,rpid

 

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