10 September 2020: Review Articles
The Role of Epigallocatechin-3-Gallate in Autophagy and Endoplasmic Reticulum Stress (ERS)-Induced Apoptosis of Human Diseases
Shuangshuang Zhang 1ABCDE* , Mengke Cao 2BCDE* , Fang Fang 3AEFG*DOI: 10.12659/MSM.924558
Med Sci Monit 2020; 26:e924558
Table 1 The role of EGCG in autophagy and human diseases.
| Disease model | Dose | EGCG Effect | References |
|---|---|---|---|
| Cancer (primary effusion lymphoma cells) | 20 μg/mL | EGCG increased LC3 transition, formation of acidic vesicular organelles, and ROS generation | 34 |
| Cancer (4T1 breast cancer cells and breast cancer xenograft) | 20 μM;20 mg kg | EGCG enhanced Beclin-1, ATG5, LC3B, and mitochondrial depolarization;EGCG reduced the weight, glucose, lactic acid, and VEGF levels in the breast cancer xenograft | 36 |
| Cancer (SSC-4 human oral squamous cells) | 20 μM | EGCG enhanced ZEB1, WNT11, IGF1R, FAS, BAK, and BAD genes and inhibited TP53, MYC, and CASP8 genes | 38 |
| Cancer (human mesothelioma cells) | 200 μM | EGCG increased the LC3-II expression levels and induced ROS | 39 |
| Cancer (glioblastoma cells) | 100 nM; 500 μM | 500 μM EGCG exhibited strong autophagy and apoptosis induction, but 100 nM had no effect. | 40 |
| Cancer (human lung A549 adenocarcinoma cells and A549 xenograft mouse model) | 80 μM;200 mg kg | EGCG inhibited LC-3 II/I ratio and AGT5, and improved p62;EGCG suppressed tumor growth and increased the survival time | 45 |
| Cancer (triple negative breast cancer cells) | 40 nmol | EGCG p53 siRNA, and EGCG activated pro-apoptotic genes and inhibited pro-survival genes, autophagy, and cell network formation | 46 |
| Cancer (HCT116 human colorectal cancer cells) | 20 μM | EGCG decreased p62 and LC3 II/I ratio to active autophagy;Inhibition of autophagy sensitized HCT116 to TRAIL-induced apoptosis on EGCG treatment | 49 |
| Cancer (oral cancer CAR cells) | 50 μM | EGCG activated ATGs, Beclin-1, and LC3B related pathway, and inhibited AKT/STAT3 signal pathway | 52 |
| Cancer (human colorectal cancer cells) | 100 μM | EGCG increased autophagosomes, acidic vesicular organelles, and LC3-II protein | 53 |
| Cancer (hepatoma hep3B cells) | 10 μg/mL | EGCG increased cell death and inhibited LC3 | 54 |
| Cancer (osteosarcoma cells) | 20 μg/mL | EGCG decreased SOX2OT variant 7 and inactivate Notch3/DLL3 signaling | 55 |
| Cancer (mouse HeLa tumor model) | 25 mg kg | EGCG induced autophagic flux and accelerated the formation of autophagosomes | 56 |
| Cancer (human pancreatic cancer PANC-1 cells and HepG2 cells) | 20, 100 μM | 20 μM EGCG increased LC3-II and reduced p-Akt in PANC-1 cells;100 μM EGCG increased LC3-II, activated caspase-3, and PARP, and reduced p-Akt in HepG2 cells | 59 |
| Neurological diseases (primary neuron cells) | 10 μM | EGCG increased LC3-II expression levels and decreased p62 levels | 65 |
| Neurological diseases (CUMS rats) | 25 mg kg | EGCG decreased p62 via mTOR/p70S6K pathway and decreased AβP1–42 levels | 66 |
| Neurological diseases (PC12 cells) | 50 μM | EGCG inhibited Ca influx, protected mitochondrial function, and downregulated Beclin-1 and AGT5 | 67 |
| Neurological diseases (PC12 cells) | 50 μM | EGCG increased LC3B and downregulated Beclin-1 | 68 |
| Diabetes (diabetic GK rats) | 100 mg kg | EGCG reduced Beclin-1 and DRP1, and reversed the phosphorylation of JNK | 71 |
| Diabetes (retinal Müller cells) | 20 μM | EGCG increased LC3-II and beclin-1, decreased P62 and improved lysosomal activity | 72 |
| Diabetes (H9c2 cardiomyoblasts) | 20 μM | EGCG restored ROS production and suppressed cytoplasmic acetylation of FoxO1 | 73 |
| Diabetes (diabetic GK rats) | 100 mg kg | EGCG enhanced autophagy signaling molecules and the FoxOs abundance | 74 |
| Cardiovascular Diseases (H9c2 cardiomyocytes) | 25 μM | EGCG inhibited autophagy through activating PI3K/Akt signals, increased miR-384 and attenuated Beclin-1 levels | 75 |
| Cardiovascular Diseases (Sprague-Dawley rats) | 10 mg kg | EGCG decreased LVEDP, CK-MB, LDH, C3-II/LC3-I ratio, Beclin-1, Atg5 and p62, and increased LVSP | 76 |
| Cardiovascular Diseases (human monocytic THP 1 cell) | 80 μM | EGCG activated autophagy via upregulating LC3B and AGT5 and stimulated cholesterol efflux via regulating class III PI3K/Beclin-1 | 77 |
| Injury (Balb/c mice) | 30 mg kg | EGCG inhibited the production of TNF-α, IL-6, IFN-γ, and IL-1β, and downregulated hepatocyte apoptosis and autophagy via IL-6/JAKs/STAT3/BNIP3 pathway | 78 |
| Injury (human retinal pigment epithelial cells) | 50 μM | EGCG inhibited UVB-induced autophagy through reducing autophagosomes and LC3-II, and activating mTOR signals | 81 |
| Bacterial Infection (cystic fibrosis) | 25 μg/mL | EGCG improved B. cenocepacia clearance by enhancing autophagy and macrophage survival, and inhibiting spread in cystic fibrosis, and promoted CFTR | 82 |
| Bacterial Infection (infected macrophages) | 50 μM | EGCG inhibited Legionella infection by rescuing autophagy genes (Atg5–Atg12 protein complex, LC3) in infected macrophages | 83 |
| EGCG – epigallocatechin-3-gallate; ROS – reactive oxygen species; VEGF – vascular endothelial growth factor; – CFRT – cystic fibrosis transmembrane conductance regulator. | |||