Drug Information

Drug (ID: DG00123) and It's Reported Resistant Information

• Name: Epigallocatechin gallate
• Target: Signal transducer and activator of transcription 3 (STAT3); STAT3_HUMAN; [1]
• Formula: C22H18O11
• IsoSMILES: C1[C@H]([C@H](OC2=CC(=CC(=C21)O)O)C3=CC(=C(C(=C3)O)O)O)OC(=O)C4=CC(=C(C(=C4)O)O)O
• InChI: 1S/C22H18O11/c23-10-5-12(24)11-7-18(33-22(31)9-3-15(27)20(30)16(28)4-9)21(32-17(11)6-10)8-1-13(25)19(29)14(26)2-8/h1-6,18,21,23-30H,7H2/t18-,21-/m1/s1
• InChIKey: WMBWREPUVVBILR-WIYYLYMNSA-N
• PubChem CID: 65064
• ChEBI ID: CHEBI:4806
• TTD Drug ID: D09CKU
• DrugBank ID: DB12116

Type(s) of Resistant Mechanism of This Drug

  EADR: Epigenetic Alteration of DNA, RNA or Protein

  MRAP: Metabolic Reprogramming via Altered Pathways

Drug Resistance Data Categorized by Their Corresponding Diseases

ICD-02: Benign/in-situ/malignant neoplasm

Osteosarcoma [ICD-11: 2B51]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-mir-126 [1]

• Sensitive Disease: Osteosarcoma [ICD-11: 2B51.0]
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• In Vitro Model: MG63 cells; Bone marrow; Homo sapiens (Human); CVCL_0426
• In Vitro Model: U2OS cells; Bone; Homo sapiens (Human); CVCL_0042
• Experiment for Molecule Alteration: Flow cytometry assay
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay
• Mechanism Description: Overexpression of miR-126 sensitizes osteosarcoma cells to apoptosis induced by epigallocatechin-3-gallate.

Lung cancer [ICD-11: 2C25]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Key Molecule: . [2]

• Metabolic Type: Glucose metabolism
• Sensitive Disease: Non-small cell lung carcinoma [ICD-11: 2C25.Y]
• Molecule Alteration: .; .
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: MAPK signaling pathway; Activation; hsa04010
• Cell Pathway Regulation: Insulin signaling pathway; Activation; hsa04910
• Cell Pathway Regulation: mTOR signaling pathway; Activation; hsa04150
• In Vitro Model: HEK 293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• In Vitro Model: Fibroblast cells; Lung; Homo sapiens (Human); N.A.
• In Vitro Model: Gefitinib-resistant NSCLC cells; Lung; Homo sapiens (Human); N.A.
• In Vitro Model: H1975 parental cells; Lung; Homo sapiens (Human); CVCL_1511
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: We found that the combined use of EGFR-TKIs and EGCG significantly reversed the Warburg effect by suppressing glycolysis while boosting mitochondrial respiration, which was accompanied by increased cellular ROS and decreased lactate secretion. The combination effectively activated the AMPK pathway while inhibited both ERK/MAPK and AKT/mTOR pathways, leading to cell cycle arrest and apoptosis, particularly in drug-resistant NSCLC cells.

Key Molecule: . [2]

• Metabolic Type: Glucose metabolism
• Sensitive Disease: Non-small cell lung carcinoma [ICD-11: 2C25.Y]
• Molecule Alteration: .; .
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: MAPK signaling pathway; Activation; hsa04010
• Cell Pathway Regulation: Insulin signaling pathway; Activation; hsa04910
• Cell Pathway Regulation: mTOR signaling pathway; Activation; hsa04150
• In Vivo Model: NCI-H1975 xenograft-bearing mice; nude mice bearing AR cell subcutaneous xenografts; Mice
• Experiment for Drug Resistance: Tumor volume assay
• Mechanism Description: We found that the combined use of EGFR-TKIs and EGCG significantly reversed the Warburg effect by suppressing glycolysis while boosting mitochondrial respiration, which was accompanied by increased cellular ROS and decreased lactate secretion. The combination effectively activated the AMPK pathway while inhibited both ERK/MAPK and AKT/mTOR pathways, leading to cell cycle arrest and apoptosis, particularly in drug-resistant NSCLC cells.

References

• Ref 1: Overexpression of miR-126 sensitizes osteosarcoma cells to apoptosis induced by epigallocatechin-3-gallate. World J Surg Oncol. 2014 Dec 16;12:383. doi: 10.1186/1477-7819-12-383.
• Ref 2: Epigallocatechin gallate circumvents drug-induced resistance in non-small-cell lung cancer by modulating glucose metabolism and AMPK/AKT/MAPK axis. Phytother Res. 2023 Dec;37(12):5837-5853.