condition found tbRes List
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


Glycolysis, Glycolysis: Click to Expand ⟱
Source:
Type:
Glycolysis is a metabolic pathway that converts glucose into pyruvate, producing a small amount of ATP (energy) in the process. It is a fundamental process for cellular energy production and occurs in the cytoplasm of cells. In normal cells, glycolysis is tightly regulated and is followed by aerobic respiration in the presence of oxygen, which allows for the efficient production of ATP.
In cancer cells, however, glycolysis is often upregulated, even in the presence of oxygen. This phenomenon is known as the Warburg Mutations in oncogenes (like MYC) and tumor suppressor genes (like TP53) can alter metabolic pathways, promoting glycolysis and other anabolic processes that support cell growth.effect.
Acidosis: The increased production of lactate from glycolysis can lead to an acidic microenvironment, which may promote tumor invasion and suppress immune responses.

Glycolysis is a hallmark of malignancy transformation in solid tumor, and LDH is the key enzyme involved in glycolysis.

Pathways:
-GLUTs, HK2, PFK, PK, PKM2, LDH, LDHA, PI3K/AKT/mTOR, AMPK, HIF-1a, c-MYC, p53, SIRT6, HSP90α, GAPDH, HBT, PPP, Lactate Metabolism, ALDO

Natural products targeting glycolytic signaling pathways https://pmc.ncbi.nlm.nih.gov/articles/PMC9631946/
Alkaloids:
-Berberine, Worenine, Sinomenine, NK007, Tetrandrine, N-methylhermeanthidine chloride, Dauricine, Oxymatrine, Matrine, Cryptolepine

Flavonoids: -Oroxyline A, Apigenin, Kaempferol, Quercetin, Wogonin, Baicalein, Chrysin, Genistein, Cardamonin, Phloretin, Morusin, Bavachinin, 4-O-methylalpinumisofavone, Glabridin, Icaritin, LicA, Naringin, IVT, Proanthocyanidin B2, Scutellarin, Hesperidin, Silibinin, Catechin, EGCG, EGC, Xanthohumol.

Non-flavonoid phenolic compounds:
Curcumin, Resveratrol, Gossypol, Tannic acid.

Terpenoids:
-Cantharidin, Dihydroartemisinin, Oleanolic acid, Jolkinolide B, Cynaropicrin, Ursolic Acid, Triptolie, Oridonin, Micheliolide, Betulinic Acid, Beta-escin, Limonin, Bruceine D, Prosapogenin A (PSA), Oleuropein, Dioscin.

Quinones:
-Thymoquinone, Lapachoi, Tan IIA, Emodine, Rhein, Shikonin, Hypericin

Others:
-Perillyl alcohol, HCA, Melatonin, Sulforaphane, Vitamin D3, Mycoepoxydiene, Methyl jasmonate, CK, Phsyciosporin, Gliotoxin, Graviola, Ginsenoside, Beta-Carotene.
Scientific Papers found: Click to Expand⟱
2459- EGCG,    Epigallocatechin gallate inhibits human tongue carcinoma cells via HK2‑mediated glycolysis
- in-vitro, Tong, Tca8113 - in-vitro, Tong, TSCCa
EGFR↓, EGCG exposure substantially decreased EGF-induced EGF receptor (EGFR), Akt and ERK1/2 activation, as well as the downregulation of hexokinase 2 (HK2).
Akt↓,
ERK↓,
HK2↓,
GlucoseCon↓, EGCG dose-dependently inhibited the consumption of glucose (Fig. 2A and B, middle) and production of lactate
lactateProd↓,
Glycolysis↓, EGCG downregulates HK2 expression and decreases human tongue carcinoma cell glycolysis.

2302- EGCG,    Flavonoids Targeting HIF-1: Implications on Cancer Metabolism
- Review, Var, NA
TumCP↓, EGCG suppressed proliferation and dose-dependently inhibited the expression of HIF-1α
Hif1a↓, EGCG significantly suppressed HIF-1α protein accumulation in these cells but did not affect HIF-1α mRNA expression.
LDHA↓, Moreover, EGCG attenuated LDHA release in Sarcoma 180 tumor-bearing mice
PFK↓, Moreover, EGCG inhibited the expression and activity of PFK in hepatocellular carcinoma (HCC-LM3 and HepG2) cells
cardioP↑, EGCG-exerted heart benefits related to reduced LDH release
Glycolysis↓, EGCG inhibits glycolysis (especially PFK activity) in aerobic glycolytic HCC cell lines
PKM2↓, EGCG inhibits glycolysis through repressing rate-limiting enzymes (PFK and PKM2)

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 - in-vitro, Nor, HPNE - in-vitro, PC, PANC1 - in-vivo, NA, NA
TumCG↓, EGCG reduced pancreatic cancer cell growth in a concentration-dependent manner
eff↑, and the growth inhibition effect was further enhanced under glucose deprivation conditions.
ROS↑, EGCG at 40 µM increased ROS levels by 1.4- and 1.6-fold in Panc-1 and MIA PaCa-2 cells, respectively
ECAR↓, EGCG affected glycolysis by suppressing the extracellular acidification rate through the reduction of the activity and levels of the glycolytic enzymes phosphofructokinase and pyruvate kinase.
ChemoSen↑, EGCG sensitized gemcitabine to inhibit pancreatic cancer cell growth in vitro and in vivo.
selectivity↑, EGCG at 80 µM for 72 h had significantly less effect on the HPNE cells, reducing cell growth by only 24%
Glycolysis↓, EGCG Inhibits Glycolysis through Suppressing Rate-Limiting Enzymes. EGCG Plus Gemcitabine Further Inhibits Glycolysis
PFK↓, EGCG treatment reduced both the activity and expression levels of phosphofructokinase (PFK) and pyruvate kinase (PK) in Panc-1 and MIA PaCa-2 cells
PKA↓,
HK2∅, EGCG failed to reduce hexokinases II (HK2) and lactate dehydrogenase A (LDHA) protein expression levels
LDHA∅,
PFKP↓, EGCG reduced the levels of PFKP and PKM2 (p < 0.01 for both) in pancreatic tumor xenograft homogenates, obtained from mice treated with EGCG
PKM2↓,
H2O2↑, EGCG at 40 µM increased H2O2 levels by 1.5- and 1.9-fold in Panc-1 and MIA PaCa-2 cells
TumW↓, EGCG and gemcitabine, given as single agents, reduced tumor weight by 40% and 52%, respectively, compared to vehicle-treated controls (p < 0.05 and p < 0.01). In combination, EGCG plus gemcitabine reduced tumor weight by 67%,

2310- EGCG,    Epigallocatechin-3-gallate downregulates PDHA1 interfering the metabolic pathways in human herpesvirus 8 harboring primary effusion lymphoma cells
- in-vitro, lymphoma, PEL
GLUT3↑, EGCG increased GLUT3 and decreased PDHA1 and GDH1 expression to disrupt glycolysis and glutaminolysis in PEL cells
PDHA1↓,
GDH↓,
ROS↑, Previously we have demonstrated that EGCG induces ROS generation and cell death in HHV8 harboring PEL cells
Glycolysis↓, EGCG induced PEL cell death may due to suppresses both the aerobic glycolysis and oxidative phosphorylation
OXPHOS↓,

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↓,

694- EGCG,    Matcha green tea (MGT) inhibits the propagation of cancer stem cells (CSCs), by targeting mitochondrial metabolism, glycolysis and multiple cell signalling pathways
- in-vitro, BC, MCF-7
Glycolysis↓, MGT might similarly act as a glycolysis inhibitor
GAPDH↓,
ROS↑, Tea cathechins may act both as anti-oxidant and as pro-oxidants
OCR↓,
ECAR↓,
mTOR↓,
OXPHOS↓,

937- EGCG,    Metabolic Consequences of LDHA inhibition by Epigallocatechin Gallate and Oxamate in MIA PaCa-2 Pancreatic Cancer Cells
- in-vitro, Pca, MIA PaCa-2
lactateProd↓, significantly reduced lactate production
Glycolysis↓,
GlucoseCon↓,
LDHA↓,

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


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 8

Results for Effect on Cancer/Diseased Cells:
Akt↓,1,   Apoptosis↑,1,   BAD↑,1,   cardioP↑,1,   Casp3↑,1,   Casp8↑,1,   Casp9↑,1,   ChemoSen↑,1,   Cyt‑c↝,1,   ECAR↓,2,   eff↑,1,   EGFR↓,2,   ERK↓,2,   GAPDH↓,1,   GDH↓,1,   GlucoseCon↓,3,   GLUT2↓,1,   GLUT3↑,1,   Glycolysis↓,8,   H2O2↑,1,   HER2/EBBR2↓,1,   Hif1a↓,1,   HK2↓,2,   HK2∅,1,   IGF-1↓,1,   lactateProd↓,3,   LDHA↓,2,   LDHA∅,1,   MAPK↓,1,   MMP↓,1,   mTOR↓,1,   NF-kB↓,1,   OCR↓,1,   OXPHOS↓,2,   cl‑PARP↑,1,   PDHA1↓,1,   PFK↓,3,   PFKP↓,1,   PKA↓,1,   PKM2↓,2,   PKM2∅,1,   p‑pRB↓,1,   Pyruv↓,1,   Raf↓,1,   RAS↓,1,   ROS↑,3,   selectivity↑,1,   TumCCA↑,2,   TumCG↓,1,   TumCP↓,2,   TumW↓,1,   Warburg↓,1,  
Total Targets: 52

Results for Effect on Normal Cells:
BioEnh↑,1,  
Total Targets: 1

Scientific Paper Hit Count for: Glycolysis, Glycolysis
8 EGCG (Epigallocatechin Gallate)
1 Chemotherapy
1 Curcumin
1 Piperine
1 Citric Acid
Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:73  Target#:129  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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