Database Query Results : EGCG (Epigallocatechin Gallate), , OCT4

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

OCT4, Octamer-binding transcription factor 4: Click to Expand ⟱

Source:

Type:

POU5F1 is a gene that encodes a transcription factor also known as Oct4.
OCT4 (Octamer-binding transcription factor 4) is a transcription factor that plays a crucial role in maintaining the pluripotency and self-renewal of embryonic stem cells. It is part of the core regulatory network that governs stem cell identity and is essential for the early stages of development.
OCT4 is often expressed in cancer stem cells, which are a subpopulation of cells within tumors that possess the ability to self-renew and drive tumorigenesis. The presence of OCT4 in these cells is associated with increased tumor aggressiveness and resistance to conventional therapies.

Scientific Papers found: Click to Expand⟱

22-

EGCG,

Inhibition of sonic hedgehog pathway and pluripotency maintaining factors regulate human pancreatic cancer stem cell characteristics

in-vitro,

PC,

CD133+

in-vitro,

PC,

CD44+

in-vitro,

PC,

CD24+

in-vitro,

PC,

ESA+

 20-60 uM

HH↓, EGCG also inhibited the components of Shh pathway (smoothened, patched, Gli1 and Gli2)
Smo↓,
PTCH1↓,
PTCH2↓,
Gli1↓,
GLI2↓,
Gli↓,
Bcl-2↓, inhibiting the expression of Bcl-2 and XIAP, and activating caspase-3
XIAP↓,
Shh↓,
survivin↓,
Casp3↑,
Casp7↑,
CSCs↓, EGCG inhibited the expression of pluripotency maintaining transcription factors (Nanog, c-Myc and Oct-4), and self-renewal capacity of pancreatic CSCs.
Nanog↓,
cMyc↓,
OCT4↓,
EMT↓, EGCG inhibited EMT by inhibiting the expression of Snail, Slug and ZEB1, and TCF/LEF transcriptional activity,
Snail↓,
Slug↓,
Zeb1↓,
TumCMig↓, significantly reduced CSC’s migration and invasion, suggesting the blockade of signaling involved in early metastasis.
TumCI↓,
eff↑, combination of quercetin with EGCG had synergistic inhibitory effects on self-renewal capacity of CSCs through attenuation of TCF/LEF and Gli activities

685-

EGCG,

CUR,

SFN,

RES,

GEN

The “Big Five” Phytochemicals Targeting Cancer Stem Cells: Curcumin, EGCG, Sulforaphane, Resveratrol and Genistein

Analysis,

NA,

Bcl-2↓,
survivin↓,
XIAP↓,
EMT↓,
Apoptosis↑,
Nanog↓,
cMyc↓,
OCT4↓,
Snail↓,
Slug↓,
Zeb1↓,
TCF↓,

4685-

EGCG,

Epigallocathechin gallate, polyphenol present in green tea, inhibits stem-like characteristics and epithelial-mesenchymal transition in nasopharyngeal cancer cell lines

in-vitro,

NPC,

TW01

in-vitro,

NPC,

TW06

CSCs↓, EGCG potently inhibited sphere formation and can eliminate the stem cell characteristics of NPC and inhibit the epithelial-mesenchymal transition (EMT) signatures.
EMT↓,
TumCMig↓, Inhibition on NPC sphere-derived cell colony formation, migration, and invasion by EGCG
TumCI↓,
OCT4↓, EGCG inhibited the expression of Klf-4 and Oct-4 in sphere-derived cells.
Snail↓, EGCG significantly inhibited the levels of Snail, Vimentin and increased E-Cadherin expression in a dose-dependent manner
Vim↓,
E-cadherin↓,
HSP70/HSPA5↓, EGCG suppresses the expression of HSP70 and HSP90, and exhibits anti-tumor activity in vitro and in vivo
HSP90↓,
AntiTum↓,

4683-

EGCG,

Epigallocatechin-3-gallate inhibits self-renewal ability of lung cancer stem-like cells through inhibition of CLOCK

in-vitro,

Lung,

A549

in-vitro,

Lung,

H1299

in-vivo,

Lung,

A549

CSCs nude mouse xenograft model

CSCs↓, it was demonstrated that EGCG suppressed the CSC-like characteristics of lung cancer cells by targeting CLOCK.
CD133↓, EGCG also decreased the ratio of CD133+ cells
CLOCK↓, The Wnt/β-catenin pathway was notably inactivated by the knockdown of CLOCK in A549 and H1299 sphere cells.
Wnt↓, Wnt/β-catenin signaling is blocked by the knockdown of CLOCK in lung CSCs
β-catenin/ZEB1↓,
CD44↓, EGCG decreased CD133, CD44, Sox2, Nanog, and Oct4 protein expression levels by targeting CLOCK
SOX2↓,
Nanog↓,
OCT4↓,

4682-

EGCG,

Human cancer stem cells are a target for cancer prevention using (−)-epigallocatechin gallate

Review,

Var,

CSCs↓, EGCG inhibits the transcription and translation of genes encoding stemness markers, indicating that EGCG generally inhibits the self-renewal of CSCs.
EMT↓, EGCG inhibits the expression of the epithelial-mesenchymal transition phenotypes of human CSCs.
ChemoSen↑, Green tea prevents human cancer, and the combination of EGCG and anticancer drugs confers cancer treatment with tissue-agnostic efficacy.
CD133↓, CD133, CD44, ALDH1A1, Nanog, Oct4
CD44↓,
ALDH1A1↓,
Nanog↓,
OCT4↓,
TumCP↓, These results show that EGCG inhibits proliferation and induces apoptosis of lung CSCs
Apoptosis↑,
p‑GSK‐3β↓, EGCG (0–100 μM) inhibited the phosphorylation of glycogen synthase kinase 3β (GSK3β) at Ser 9, which significantly increases the expression of GSK3β, and decreases the expression of β-catenin and its downstream target gene c-Myc.
GSK‐3β↑,
β-catenin/ZEB1↓,
cMyc↓,
XIAP↓, EGCG (30–60 μM) inhibits the expression of X-linked inhibitor of apoptosis protein (XIAP), Bcl2, and survivin as well as that of the EMT markers vimentin, Slug, Snail, and nuclear β-catenin.
Bcl-2↓,
survivin↓,
Vim↓,
Slug↓,
Snail↓,

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 5

Pathway results for Effect on Cancer / Diseased Cells:

Functional Outcomes ⓘ

AntiTum↓, 1,
Total Targets: 42

Pathway results for Effect on Normal Cells:

Total Targets: 0

Scientific Paper Hit Count for: OCT4, Octamer-binding transcription factor 4

5 EGCG (Epigallocatechin Gallate)
1 Curcumin
1 Sulforaphane (mainly Broccoli)
1 Resveratrol
1 Genistein (soy isoflavone)

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#:508  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

Database Query Results : EGCG (Epigallocatechin Gallate), , OCT4

Pathway results for Effect on Cancer / Diseased Cells:

Mitochondria & Bioenergetics ⓘ

Core Metabolism/Glycolysis ⓘ

Cell Death ⓘ

Protein Folding & ER Stress ⓘ

Proliferation, Differentiation & Cell State ⓘ

Migration ⓘ

Drug Metabolism & Resistance ⓘ

Functional Outcomes ⓘ

Pathway results for Effect on Normal Cells:

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