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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 |
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| Cyclin E regulates multiple downstream molecules, such as the retinoblastoma susceptibility gene (RB1) and the transcription factor E2F. Cyclin E is a prognostic marker in breast cancer, its altered expression increased with the increasing stage and grade of the tumor. Cyclin E is a regulatory protein that plays a critical role in the cell cycle, particularly in the transition from the G1 phase to the S phase. Its expression levels can significantly influence cancer progression and patient prognosis. Cyclin E expression is frequently elevated in various cancers and is generally associated with poor prognosis. Its role in promoting cell cycle progression makes it a potential biomarker for tumor aggressiveness and patient outcomes. |
| 3238- | EGCG, | Green tea catechin, epigallocatechin-3-gallate (EGCG): mechanisms, perspectives and clinical applications |
| - | Review, | Var, | NA |
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