EGCG (Epigallocatechin Gallate) / ER Stress Cancer Research Results

EGCG, EGCG (Epigallocatechin Gallate): Click to Expand ⟱
Features:

Epigallocatechin-3-gallate — EGCG is a naturally occurring galloylated flavan-3-ol and the quantitatively dominant catechin in green tea leaves from Camellia sinensis. It is formally classified as a dietary polyphenol, catechin and investigational pleiotropic bioactive compound. EGCG has concentration-, oxidation-, metal- and cellular-context-dependent activity: it can function as an antioxidant and NRF2-associated cytoprotective agent in normal tissues, but may generate reactive oxygen species and induce stress-mediated death in susceptible cancer cells. It is not an approved anticancer drug, and purified high-dose extracts are pharmacologically and toxicologically distinct from brewed green tea.

Primary mechanisms (ranked):

  1. Biphasic redox modulation, including direct radical scavenging and metal chelation at lower exposure, but auto-oxidation, hydrogen-peroxide generation and pro-oxidant stress under permissive cancer-cell culture conditions.
  2. Suppression of proliferative and survival signalling, particularly PI3K–AKT–mTOR, NF-κB, receptor tyrosine kinase, STAT and context-dependent MAPK pathways.
  3. Mitochondrial dysfunction and intrinsic apoptosis through mitochondrial membrane-potential loss, cytochrome-c release and caspase activation.
  4. Cell-cycle arrest through modulation of cyclins, cyclin-dependent kinases, p21, p27 and p53-associated signalling.
  5. Inhibition of invasion, epithelial–mesenchymal transition and extracellular-matrix degradation through reduced FAK, MMP-2, MMP-9, uPA and related motility pathways.
  6. Suppression of HIF-1α–VEGF signalling, angiogenesis and hypoxia adaptation.
  7. Metabolic disruption involving reduced glycolysis, glucose transport and context-dependent mitochondrial energy production.
  8. Epigenetic modulation, including experimental inhibition or altered expression of DNMTs, HDACs and EZH2.
  9. Modulation of proteostasis, autophagy, endoplasmic-reticulum stress and unfolded-protein responses.
  10. NRF2 activation as a secondary adaptive mechanism, generally cytoprotective in normal cells but potentially protective or treatment-resistant in some cancers.
  11. Chemosensitization or radiosensitization in selected experimental models; treatment protection, antagonism or normal-tissue radioprotection can also occur depending on dose, schedule and therapy.

Bioavailability / PK relevance: Oral bioavailability is low and highly variable because EGCG is chemically unstable near neutral or alkaline pH, has limited intestinal permeability, undergoes extensive methylation, glucuronidation and sulfation, and is influenced by food and microbiota. Plasma concentrations after tea consumption are usually submicromolar, while large supplemental doses may transiently produce low-micromolar exposure. Fasting can increase systemic exposure but may also increase hepatic toxicity risk. Nanoencapsulation, lipid carriers and other delivery systems improve exposure experimentally but are not established anticancer treatments.

In-vitro vs systemic exposure relevance: Many anticancer experiments use approximately 10–100 µM EGCG, whereas conventional oral administration generally produces submicromolar to low-micromolar plasma concentrations. Thus, many direct cytotoxic, glycolytic, mitochondrial and kinase effects occur at concentrations substantially exceeding typical achievable systemic exposure. EGCG can also oxidize in culture media and generate extracellular hydrogen peroxide, creating experimental effects that may not translate directly in vivo.

Clinical evidence status: Extensive preclinical evidence; multiple small human biomarker, prevention and early-phase studies; limited randomized evidence for selected premalignant or recurrence-prevention settings; no established therapeutic efficacy against active cancer and no regulatory approval as an anticancer agent. A recent randomized colorectal adenoma study reported reduced recurrence, but this does not establish treatment efficacy for invasive colorectal cancer. Ongoing clinical studies continue to investigate prevention and adjunctive applications.

Safety and interactions: Brewed green tea is generally well tolerated, whereas concentrated green-tea extracts and purified EGCG have been associated with dose-dependent aminotransferase elevations and rare clinically significant liver injury. Doses around 800 mg EGCG per day have generated a regulatory safety signal, and a universally safe supplemental dose has not been established. Risk may be higher with fasting administration, pre-existing liver disease or multi-ingredient weight-loss products. EGCG can bind non-heme iron, alter drug transporters or metabolic enzymes, and modify exposure to some medications; oncology use should therefore be reviewed for drug-specific interactions.



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). FDA says <800mg/day (hepatotoxicity)
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

EGCG Mechanistic Profile

Rank Pathway / Axis Cancer Cells Normal Cells TSF Primary Effect Notes / Interpretation
1 Biphasic redox modulation ↑ ROS or ↓ ROS (dose-dependent) (context-dependent) ↓ ROS; ↑ antioxidant buffering P–R Oxidative stress or antioxidant protection Auto-oxidation and metal-catalysed peroxide formation may drive cancer-cell toxicity; culture-medium oxidation can exaggerate this mechanism.
2 PI3K AKT mTOR survival signalling ↓ PI3K; ↓ AKT; ↓ mTOR ↔ or adaptive modulation R–G Reduced proliferation and survival Frequently reported across models, but direct target engagement at physiologically achievable concentrations remains uncertain.
3 Mitochondrial apoptosis ↓ ΔΨm; ↑ cytochrome c; ↑ caspase-9; ↑ caspase-3; ↑ PARP cleavage ↔ or preserved mitochondrial function R–G Intrinsic apoptotic death Usually downstream of redox stress, calcium disturbance or survival-pathway inhibition.
4 NF-κB inflammatory survival signalling ↓ NF-κB; ↓ COX-2; ↓ inflammatory cytokines ↓ pathological inflammation R–G Reduced inflammatory and anti-apoptotic transcription Potentially relevant to tumour-promoting inflammation and treatment resistance.
5 Cell-cycle regulation ↓ cyclin D1; ↓ cyclin E; ↓ CDK2; ↓ CDK4; ↓ CDK6; ↑ p21; ↑ arrest ↔ or transient arrest G Cytostatic growth inhibition Arrest may occur at G1, S or G2/M depending on tumour type and concentration.
6 Invasion EMT and matrix remodelling ↓ EMT; ↓ FAK; ↓ uPA; ↓ MMP-2; ↓ MMP-9; ↓ migration ↔ G Reduced invasion and metastatic phenotype Predominantly supported by cellular and animal models.
7 HIF-1α VEGF angiogenesis axis ↓ HIF-1α; ↓ VEGF; ↓ angiogenic signalling ↔ or context-dependent vascular protection G Reduced hypoxia adaptation and angiogenesis Responses depend on oxygen tension, cell type and exposure.
8 Glycolysis and energy metabolism ↓ GLUT1; ↓ HK2; ↓ PKM2; ↓ LDHA; ↓ ECAR; ↓ ATP (model-dependent) ↔ or improved metabolic homeostasis R–G Metabolic stress Many metabolic findings use concentrations above typical human plasma exposure.
9 Calcium ER stress and proteostasis ↑ Ca²⁺; ↑ ER stress; ↑ UPR; ↑ GRP78 (context-dependent) ↔ or ↓ pathological ER stress P–G Proteotoxic stress and apoptosis GRP78 and UPR activation may promote death or adaptation depending on intensity and duration.
10 Epigenetic regulation ↓ DNMT activity; ↓ HDAC signalling; ↓ EZH2 (model-dependent) ↔ G Re-expression of suppressed genes Biochemical inhibition and intracellular effects may require different concentrations.
11 NRF2 antioxidant response ↑ NRF2 or ↔ (context-dependent) ↑ NRF2; ↑ HO-1; ↑ GSH; ↑ antioxidant enzymes R–G Secondary adaptive cytoprotection NRF2 can protect normal tissue but may also counteract EGCG-induced oxidative injury or support resistant cancer cells.
12 Cancer stemness signalling ↓ Wnt β-catenin; ↓ Hedgehog GLI; ↓ Notch; ↓ stem-cell markers ↔ G Reduced self-renewal phenotype Evidence remains predominantly preclinical and model-dependent.
13 Chemosensitization ↑ treatment response or ↓ resistance (drug-dependent) ↔ or ↑ tissue protection R–G Adjunctive modulation Reported with several cytotoxic and targeted agents, but EGCG can also alter drug absorption, transport or stability; combinations require individual evaluation.
14 Radiosensitization and radioprotection ↑ radiosensitivity or ↔ (schedule-dependent) ↓ radiation injury in some models R–G Context-dependent radiation modulation Opposing tumour and normal-tissue effects are possible; clinical evidence is insufficient for routine supplementation during radiotherapy.
15 Clinical Translation Constraint Effective experimental exposure often not systemically achievable ↑ hepatic risk with concentrated high-dose extracts G Limited clinical translation Poor oral bioavailability, rapid metabolism, instability, formulation heterogeneity, fasting-related exposure, liver toxicity and limited definitive oncology trials constrain deployment.

P: 0–30 min    R: 30 min–3 hr    G: >3 hr



Alzheimer’s disease relevance: EGCG has substantial preclinical neuroprotective evidence but no established clinical efficacy for Alzheimer’s disease. Proposed actions include inhibition or remodelling of amyloid-β aggregation, altered amyloid precursor protein processing, metal chelation, reduced tau-associated injury, suppression of neuroinflammation, mitochondrial protection and activation of NRF2-associated antioxidant defences. Most positive findings derive from biochemical, cellular or animal models, and brain exposure after conventional oral administration is uncertain. EGCG should therefore be classified as preclinical or exploratory for Alzheimer’s disease rather than as a validated disease-modifying therapy.

EGCG in Alzheimer’s Disease

Rank Pathway / Axis Modulation Primary Effect Notes / Interpretation
1 Amyloid beta aggregation ↓ fibril formation; ↑ non-toxic aggregate remodelling Reduced amyloid-associated toxicity Strong biochemical and preclinical rationale; effective brain exposure in humans remains uncertain.
2 Amyloid precursor protein processing ↑ non-amyloidogenic processing; ↓ amyloidogenic burden (model-dependent) Reduced amyloid generation Primarily demonstrated in cellular and animal systems.
3 Neuroinflammation ↓ NF-κB; ↓ NLRP3; ↓ inflammatory cytokines; ↓ microglial activation Reduced inflammatory neurotoxicity Inflammatory effects are context-, model- and dose-dependent.
4 Oxidative stress and NRF2 ↓ ROS; ↑ NRF2; ↑ HO-1; ↑ endogenous antioxidant defence Neuronal cytoprotection Antioxidant signalling is more relevant at achievable exposure than many direct cytotoxic cancer mechanisms.
5 Mitochondrial function ↑ membrane stability; ↑ ATP preservation; ↓ mitochondrial ROS Improved neuronal bioenergetics Supported mainly by experimental injury and transgenic models.
6 Tau pathology ↓ tau phosphorylation or aggregation (model-dependent) Reduced cytoskeletal and synaptic injury Less developed evidence base than amyloid-related mechanisms.
7 Metal homeostasis ↓ redox-active iron and copper interactions Reduced metal-promoted aggregation and oxidative injury Chelation may contribute mechanistically but could also impair dietary non-heme iron absorption.
8 Clinical Translation Constraint ↓ oral and brain exposure; ↑ formulation variability Uncertain human efficacy No convincing evidence currently establishes EGCG as an Alzheimer’s disease-modifying treatment.


ER Stress, endoplasmic reticulum (ER) stress signaling pathway: Click to Expand ⟱
Source:
Type:
Protein expression of ATF, GRP78, and GADD153 which is a hall marker of ER stress.
The endoplasmic reticulum (ER) stress signaling pathway plays a crucial role in maintaining cellular homeostasis and responding to various stressors, including those encountered in cancer. When cells experience stress, such as the accumulation of misfolded proteins, they activate a series of signaling pathways collectively known as the unfolded protein response (UPR). The UPR aims to restore normal function by enhancing the protein-folding capacity of the ER, degrading misfolded proteins, and, if the stress is unresolved, triggering apoptosis.
The activation of ER stress pathways can contribute to resistance against chemotherapy and targeted therapies. Cancer cells may utilize the UPR to survive treatment-induced stress, making it challenging to achieve effective therapeutic outcomes.

-ER stress-associated proteins include: phosphorylation of PERK, eIF2α, ATF4, CHOP and cleaved-caspase 12
Scientific Papers found: Click to Expand⟱
6124- CHr,  EGCG,    The anticancer flavonoid chrysin induces the unfolded protein response in hepatoma cells
- in-vitro, HCC, HepG2
TumCG↓, report that chrysin inhibits hepatoma cells growth and induces apoptosis in a dose-dependent manner.
Apoptosis↓,
GRP78/BiP↑, Chrysin induces GRP78 overexpression, X-box binding protein-1 splicing and eukaryotic initiation factor 2α phosphorylation, hallmarks of the unfolded protein response.
eff↑, GRP78 knockdown potentiates chrysin-induced caspase-7 cleavage in hepatoma cells and enhances chrysin-induced apoptosis.
cl‑Casp7↑,
cl‑PARP↑, Combination of EGCG potentiates chrysin-induced caspase-7 and poly (ADP-ribose) polymerase (PARP) cleavage.
eff↑, Finally, EGCG sensitizes hepatoma cells to chrysin through caspase-mediated apoptosis
UPR↑, data suggest that chrysin triggers the unfolded protein response. Chrysin induces the unfolded protein response
ER Stress↑, Chrysin can induce ER stress response in hepatoma cells, including up-regulation of GRP78 expression, induction of eIF-2α phosphorylation and XBP-1 splicing.
p‑eIF2α↑,
XBP-1↝,
Proteasome↓, Chrysin is a known proteasome inhibitor [27]

3202- EGCG,    Epigallocatechin-3-gallate enhances ER stress-induced cancer cell apoptosis by directly targeting PARP16 activity
- in-vitro, Cerv, HeLa - in-vitro, HCC, QGY-7703
PARP16↓, (EGCG) as a potential inhibitor of PARP16.
p‑PERK↓, EGCG suppressed the ER stress-induced phosphorylation of PERK and the transcription of unfolded protein response-related genes,
Apoptosis↑, leading to dramatically increase of cancer cells apoptosis
eIF2α↓, EGCG suppressed the phosphorylation of PERK and eIF2α induced by ER stress.
UPR↓, UPR-related gene was dramatically induced by BFA and TUN, and this induction was suppressed by treatment of Hela cells with EGCG, further suggesting that EGCG suppressed the UPR induced by ER stress.
ER Stress↑, EGCG can dramatically inhibit the activity of PARP16, and then suppressed the ER stress-induced PERK phosphorylation, leading to dramatical increase of the ER stress-induced apoptosis of cancer cells.
eff↑, These results indicate that EGCG can be used in combination with ER stress-induced drugs to treat the cancer cell.
GRP78/BiP↓, EGCG had previously been found to bind to the ATP-binding domain of glucose regulate protein 78 (GRP78),

3204- EGCG,    The Role of ER Stress and the Unfolded Protein Response in Cancer
- Review, Var, NA
BID↓, EGCG, a green tea polyphenol, induces ER stress-mediated apoptosis in colorectal cancer cells, an effect associated with BiP upregulation
UPR↑, Natural compounds have also been identified as BiP modulators, including palmatine and epigallocatechin gallate (EGCG), which impair BiP function, leading to unfolded protein accumulation and UPR activation.
ER Stress↑,

3205- EGCG,    The Role of Epigallocatechin-3-Gallate in Autophagy and Endoplasmic Reticulum Stress (ERS)-Induced Apoptosis of Human Diseas
- Review, Var, NA - Review, AD, NA
Beclin-1↑, EGCG not only regulates autophagy via increasing Beclin-1 expression and reactive oxygen species generation,
ROS↑,
Apoptosis↑, Apoptosis is a common cell function in biology and is induced by endoplasmic reticulum stress (ERS)
ER Stress↑,
*Inflam↓, EGCG has health benefits including anti-tumor [15], anti-inflammatory [16], anti-diabetes [17], anti-myocardial infarction [18], anti-cardiac hypertrophy [19], anti-atherosclerosis [20], and antioxidant
*cardioP↑,
*antiOx↑,
*LDL↓, These effects are mainly related to (LDL) cholesterol inhibition, NF-κB inhibition, MPO activity inhibition, decreased levels of glucose and glycated hemoglobin in plasma, decreased inflammatory markers, and reduced ROS generation
*NF-kB↓,
*MPO↓,
*glucose↓,
*ROS↓,
ATG5↑, EGCG induced autophagy by enhancing Beclin-1, ATG5, and LC3B and promoted mitochondrial depolarization in breast cancer cells.
LC3B↑,
MMP↑,
lactateProd↓, 20 mg kg−1 EGCG significantly decreased glucose, lactic acid, and vascular endothelial growth factor (VEGF) levels
VEGF↓,
Zeb1↑, (20 uM) inhibited the proliferation through activating autophagy via upregulating ZEB1, WNT11, IGF1R, FAS, BAK, and BAD genes and inhibiting TP53, MYC, and CASP8 genes in SSC-4 human oral squamous cells [
Wnt↑,
IGF-1R↑,
Fas↑,
Bak↑,
BAD↑,
TP53↓,
Myc↓,
Casp8↓,
LC3II↑, increasing the LC3-II expression levels and induced apoptosis via inducing ROS in mesothelioma cell lines,
NOTCH3↓, but also could reduce partially Notch3/DLL3 to reduce drug-resistance and the stemness of tumor cells
eff↑, In combination therapies, low-intensity pulsed electric field (PEF) can improve EGCG to affect tumor cells; ultrasound (US) with tumor cells is the application of physical stimulation in cancer therapy.
p‑Akt↓, 20 μM EGCG increased intracellular ROS levels and LC3-II, and inhibited p-Akt in PANC-1 cells
PARP↑, 100 μM EGCG increased LC3-II, activated caspase-3 and PARP, and reduced p-Akt in HepG2
*Cyt‑c↓, EGCG protected neuronal cells against human viruses by inhibiting cytochrome c and Bax translocations, and reducing autophagy with increased LC3-II expression and decreased p62 expression
*BAX↓,
*memory↑, EGCG restored autophagy in the mTOR/p70S6K pathway to weaken memory and learning disorders induced by CUMS
*neuroP↑, Finally, EGCG increased the neurological scores through inhibiting cell death
*Ca+2?, EGCG treatment, [Ca2+]m and [Ca2+]i expressions were reduced and oxyhemoglobin-induced mitochondrial dysfunction lessened.
GRP78/BiP↑, MMe cells with EGCG treatment improved GRP78 expression in the endoplasmic reticulum, and induced EDEM, CHOP, XBP1, and ATF4 expressions, and increased the activity of caspase-3 and caspase-8.
CHOP↑, GRP78 accumulation converted UPR of MMe cells into pro-apoptotic ERS
ATF4↑,
Casp3↑,
Casp8↑,
UPR↑,

3206- EGCG,    Insights on the involvement of (-)-epigallocatechin gallate in ER stress-mediated apoptosis in age-related macular degeneration
- Review, AMD, NA
*Ca+2↓, EGCG restores [Ca2+]i homeostasis by decreasing ROS production through inhibition of prohibitin1 which regulate ER-mitochondrial tether site and inhibit apoptosis.
*ROS↓,
*Apoptosis↓,
*GRP78/BiP↓, EGCG downregulated GRP78, CHOP, PERK, ERO1α, IRE1α, cleaved PARP, cleaved caspase 3, caspase 12 and upregulated expression of calnexinin MRPE cells
*CHOP↓,
*PERK↓,
*IRE1↓,
*p‑PARP↓,
*Casp3↓,
*Casp12↓,
*ER Stress↓,
*UPR↓, EGCG mitigates ER stress; maintain calcium homeostasis and inhibition of UPR to control the progression of AMD.

3207- EGCG,    EGCG Enhances the Chemosensitivity of Colorectal Cancer to Irinotecan through GRP78-MediatedEndoplasmic Reticulum Stress
- in-vitro, CRC, RKO - in-vitro, CRC, HCT116
GRP78/BiP↑, Findings showed that EGCG alone or in combination with irinotecan can significantly promote intracellular GRP78 protein expression, reduce mitochondrial membrane potential and intracellular ROS in RKO and HCT 116 cells
MMP↓,
ER Stress↑, activate ERS of colorectal cancer cells,
ROS↓, EGCG Alone and in Combination with Irinotecan Inhibit ROS Production in CRC
UPR↑, EGCG can promote the transformation of constitutive UPR of colorectal cancer cells into endoplasmic reticulum stress by increasing the accumulation of intracellular GRP78 and inhibiting its cell membrane translocation.

3208- EGCG,    Induction of Endoplasmic Reticulum Stress Pathway by Green Tea Epigallocatechin-3-Gallate (EGCG) in Colorectal Cancer Cells: Activation of PERK/p-eIF2α/ATF4 and IRE1α
- in-vitro, Colon, HT29 - in-vitro, Nor, 3T3
TumCD↓, EGCG treatment was toxic to the HT-29 cell line
ER Stress↑, EGCG induced ER stress in HT-29 by upregulating immunoglobulin-binding (BiP), PKR-like endoplasmic reticulum kinase (PERK), phosphorylation of eukaryotic initiation factor 2 alpha subunit (eIF2α), activating transcription 4 (ATF4), and IRE1α
GRP78/BiP↑,
PERK↑,
eIF2α↑,
ATF4↑,
IRE1↑,
Apoptosis↑, Apoptosis was induced in HT-29 cells after the EGCG treatment, as shown by the Caspase 3/7 activity.
Casp3↑,
Casp7↑,
Wnt↓, (CRC) via suppression of the Wnt/β-catenin pathway
β-catenin/ZEB1↓,
*toxicity∅, This embryonic fibroblast cell line (3T3) has shown that the EGCG was not toxic to normal healthy cells, given the treatment at any concentration even at the highest concentration of EGCG (1000 μM).
UPR↑, ER stress is induced by EGCG and activates UPR proteins

677- EGCG,    Induction of Endoplasmic Reticulum Stress Pathway by Green Tea Epigallocatechin-3-Gallate (EGCG) in Colorectal Cancer Cells: Activation of PERK/p-eIF2 α /ATF4 and IRE1 α
- in-vitro, CRC, HT-29
ER Stress↑,
GRP78/BiP↑,
PERK↑,
eIF2α↑,
ATF4↑,
IRE1↑, IRE1 α
Apoptosis↑,

6784- EGCG,    Dietary (−)-Epigallocatechin Gallate (EGCG): State-of-the-Art Advances in Bioactivities, Bioavailability Enhancement Strategies, and Applications in Nutrition and Health
- Review, Nor, NA
*antiOx↑, bioactivities of EGCG, including its antioxidant, anti-inflammatory, anticancer, cardiovascular protective, metabolic regulatory, neuroprotective, gut microbiota-modulating, and antimicrobial properties.
*Inflam↓,
*AntiCan↑,
*cardioP↑,
*neuroP↑,
*GutMicro↑,
*AntiBio↑,
*ROS↓, Figure 1, anti inflammatory
*TNF-α↓,
*IL6↓,
TumCP↓,
*LDL↓, cardioprotective
*NO↓,
*Obesity↓, Metabolic syndrome
*p‑tau↓, nervous system
*Aβ↓,
*NRF2↑, , EGCG has been shown to activate the Keap1/P62/Nrf2 signaling pathway,
*SOD↑, upregulation of endogenous antioxidant enzymes, such as superoxide dismutase, catalase, and glutathione peroxidase, indirectly diminishing the levels of intracellular oxygen free radicals
*Catalase↑,
*GPx↑,
*NLRP3↓, EGCG also restores autophagy levels, suppresses the activation of the NLRP3 inflammasome by inhibiting the mammalian target of rapamycin signaling pathway
*mTOR↓,
TumCCA↑, Cancer: induce cell cycle arrest and inhibit tumor cell proliferation
NRF2↓, EGCG inhibits CCL5-stimulated lung cancer cell proliferation by down-regulating Nrf2 expression
Apoptosis↑, Inducing Apoptosis in Cancer Cells
SIRT1↓, EGCG activates the mitochondrial apoptotic pathway by downregulating SIRT1 expression to modulate the SIRT1-p53 axis
miR-25-5p↓, In breast cancer, EGCG induces apoptosis by inhibiting miR-25 expression and elevating PARP, pre-caspase-3 and pre-caspase-9 protein levels
PARP↑,
Casp3↑,
Casp9↑,
ER Stress↑, in multiple myeloma, EGCG promotes apoptosis by activating the endoplasmic reticulum stress pathway
TumAuto↑, EGCG induces autophagic cell death in breast cancer cells by retaining YAP1 in the cytoplasm and promoting the assembly of the CHMP2B-VPS4B complex
EMT↓, EGCG has been demonstrated to inhibit EMT, invasion, and migration by blocking the TGFβ/Smad signaling pathway
TumCI↓,
TumCMig↓,
TGF-β↓,
Smad1↓,
STAT3↓, EGCG can directly bind to STAT3, reducing nuclear localization and inhibiting the transcription of PLXNC1.
VEGF↓, widely believed that EGCG can block this process by reducing the expression of vascular endothelial growth factor, a key factor in angiogenesis,
angioG↓, The inhibition of angiogenic mimicry by EGCG through the Twist/VE-calmodulin/AKT pathway has also been demonstrated in prostate cancer cells
Imm↑, Acting as an Immunomodulator
EGFR↓, EGCG possesses the ability to interact with EGFR and inhibit activity, strengthening the anticancer evidence for EGCG
*GutMicro↑, EGCG can regulate the balance of gut flora. For example, EGCG can inhibit the growth of harmful bacteria such as Escherichia coli and Salmonella, while promoting the proliferation of probiotics like Bifidobacterium and Lactobacillus
*Bacteria↓, Antibacterial and Antiviral Properties of EGCG
*AntiViral↑,
*BioAv↓, EGCG, its low bioavailability in the human body limits clinical efficacy.
*BioAv↑, Nanotechnology strategy of EGCG.
*eff↑, Co-encapsulation assay of EGCG with quercetin shows that the two synergistically enhanced the antioxidant capacity of EGCG
*BioAv↑, Combining EGCG with resveratrol increases its solubility and significantly improves its absorption in the small intestine.
eff↑, combination of EGCG and curcumin inhibits the activity of metabolic enzymes, reduces the rate of metabolism in the liver and enhances its antitumor efficacy
ChemoSen↑, synergistic effects of EGCG combined with chemotherapeutic agents such as 5-fluorouracil, celecoxib, cisplatin, and tamoxifen have also been reported
*toxicity↝, The European Food Safety Authority notes in scientific opinion that daily oral doses of 800 mg or higher of EGCG represent a common starting point for observed cases of liver injury


Showing Research Papers: 1 to 9 of 9

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 9

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress(tgid=1) ⓘ

NRF2↓, 1,   ROS↓, 1,   ROS↑, 1,  

Mitochondria & Bioenergetics(tgid=3) ⓘ

MMP↓, 1,   MMP↑, 1,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

lactateProd↓, 1,   SIRT1↓, 1,  

Cell Death(tgid=5) ⓘ

p‑Akt↓, 1,   Apoptosis↓, 1,   Apoptosis↑, 5,   BAD↑, 1,   Bak↑, 1,   BID↓, 1,   Casp3↑, 3,   Casp7↑, 1,   cl‑Casp7↑, 1,   Casp8↓, 1,   Casp8↑, 1,   Casp9↑, 1,   Fas↑, 1,   Myc↓, 1,   Proteasome↓, 1,   TumCD↓, 1,  

Kinase & Signal Transduction(tgid=6) ⓘ

miR-25-5p↓, 1,  

Protein Folding & ER Stress(tgid=8) ⓘ

CHOP↑, 1,   eIF2α↓, 1,   eIF2α↑, 2,   p‑eIF2α↑, 1,   ER Stress↑, 8,   GRP78/BiP↓, 1,   GRP78/BiP↑, 5,   IRE1↑, 2,   PERK↑, 2,   p‑PERK↓, 1,   UPR↓, 1,   UPR↑, 5,   XBP-1↝, 1,  

Autophagy & Lysosomes(tgid=9) ⓘ

ATG5↑, 1,   Beclin-1↑, 1,   LC3B↑, 1,   LC3II↑, 1,   TumAuto↑, 1,  

DNA Damage & Repair(tgid=10) ⓘ

PARP↑, 2,   cl‑PARP↑, 1,   TP53↓, 1,  

Cell Cycle & Senescence(tgid=11) ⓘ

TumCCA↑, 1,  

Proliferation, Differentiation & Cell State(tgid=12) ⓘ

EMT↓, 1,   IGF-1R↑, 1,   NOTCH3↓, 1,   STAT3↓, 1,   TumCG↓, 1,   Wnt↓, 1,   Wnt↑, 1,  

Migration(tgid=13) ⓘ

Smad1↓, 1,   TGF-β↓, 1,   TumCI↓, 1,   TumCMig↓, 1,   TumCP↓, 1,   Zeb1↑, 1,   β-catenin/ZEB1↓, 1,  

Angiogenesis & Vasculature(tgid=14) ⓘ

angioG↓, 1,   ATF4↑, 3,   EGFR↓, 1,   VEGF↓, 2,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

Imm↑, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

ChemoSen↑, 1,   eff↑, 5,  

Clinical Biomarkers(tgid=22) ⓘ

EGFR↓, 1,   Myc↓, 1,   TP53↓, 1,  

Functional Outcomes(tgid=23) ⓘ

PARP16↓, 1,  
Total Targets: 71

Pathway results for Effect on Normal Cells:


NA, unassigned(tgid=0) ⓘ

AntiBio↑, 1,  

Redox & Oxidative Stress(tgid=1) ⓘ

antiOx↑, 2,   Catalase↑, 1,   GPx↑, 1,   MPO↓, 1,   NRF2↑, 1,   ROS↓, 3,   SOD↑, 1,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

glucose↓, 1,   LDL↓, 2,  

Cell Death(tgid=5) ⓘ

Apoptosis↓, 1,   BAX↓, 1,   Casp12↓, 1,   Casp3↓, 1,   Cyt‑c↓, 1,  

Protein Folding & ER Stress(tgid=8) ⓘ

CHOP↓, 1,   ER Stress↓, 1,   GRP78/BiP↓, 1,   IRE1↓, 1,   PERK↓, 1,   UPR↓, 1,  

DNA Damage & Repair(tgid=10) ⓘ

p‑PARP↓, 1,  

Proliferation, Differentiation & Cell State(tgid=12) ⓘ

mTOR↓, 1,  

Migration(tgid=13) ⓘ

Ca+2?, 1,   Ca+2↓, 1,  

Angiogenesis & Vasculature(tgid=14) ⓘ

NO↓, 1,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

IL6↓, 1,   Inflam↓, 2,   NF-kB↓, 1,   TNF-α↓, 1,  

Synaptic & Neurotransmission(tgid=18) ⓘ

p‑tau↓, 1,  

Protein Aggregation(tgid=19) ⓘ

Aβ↓, 1,   NLRP3↓, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

BioAv↓, 1,   BioAv↑, 2,   eff↑, 1,  

Clinical Biomarkers(tgid=22) ⓘ

GutMicro↑, 2,   IL6↓, 1,  

Functional Outcomes(tgid=23) ⓘ

AntiCan↑, 1,   cardioP↑, 2,   memory↑, 1,   neuroP↑, 2,   Obesity↓, 1,   toxicity↝, 1,   toxicity∅, 1,  

Infection & Microbiome(tgid=24) ⓘ

AntiViral↑, 1,   Bacteria↓, 1,  
Total Targets: 47

Scientific Paper Hit Count for: ER Stress, endoplasmic reticulum (ER) stress signaling pathway
9 EGCG (Epigallocatechin Gallate)
1 Chrysin
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#:103  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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