Lecture Notes: EGCG and Cancer as a Mitochondrial Metabolic Disease

Introduction to EGCG

• EGCG (Epigallocatechin gallate) is a catechin, a type of flavonoid found in green tea.
• Known for potential health benefits, especially in cancer treatment.
• Unlike other natural glutamine inhibitors, EGCG works on glutamine enzymes within the cell and TCA cycle.

EGCG and Cancer

• Demonstrates anti-proliferative, anti-angiogenic, and pro-apoptotic effects.
• Interrupts signaling pathways associated with cancer cell proliferation and division.
• Interferes with cancer hallmarks:
  • Genomic instability
  • Anti-apoptosis mechanisms
  • Tumor genesis
  • Sustained proliferative signaling
  • Evasion of growth suppressors
  • Deregulated cell metabolism
  • Tumor promoting inflammation
  • Induction of angiogenesis
  • Tissue invasion and metastasis
  • Immune invasion

Mechanisms of EGCG

• Adherence, Migration, and Extracellular Matrix Remodeling:
  • Affects TGF beta and multiple signaling pathways.
• Anti-angiogenesis:
  • Affects vascular endothelial growth factor pathway.
  • Inhibits HIF1 Alpha, mTOR, PI3K/AKT pathway, and more.
• Blocks SMAD and glutathione synthesis pathways.
• Impacts inflammatory cytokines and chemokines.

EGCG in Metabolic Pathways

• Suppresses metabolic reprogramming pathways:
  • Glucose uptake
  • Aerobic glycolysis (Warberg effect)
  • Glutamine metabolism
  • Fatty acid metabolism
  • Nucleotide synthesis

Specific Actions on Metabolic Pathways

• Blocks several enzymes and pathways:
  • PFK (phosphofructokinase) in glycolysis
  • Lactate dehydrogenase
  • G6PD affecting pentose phosphate pathway
  • FASN enzyme for fatty acid creation
  • PI3K/AKT pathway, HIF1 Alpha, mTOR
  • Glutamate dehydrogenase enzyme
  • Alpha-ketoglutarate conversion

EGCG vs. Other Inhibitors

• EGCG compared with DON:
  • Both inhibit glutamine metabolism.
  • EGCG shows significant dose-response curve.
  • Comparable effectiveness to DON, with slight edge for DON.

Conclusion

• EGCG is a highly effective, safe, and accessible tool against cancer.
• Can be consumed through green tea or supplementation.
• Always consult with healthcare provider before starting any new intervention.

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Takeaways

• 🌿 EGCG's Potential Health Benefits: Found in green tea, EGCG (Epigallocatechin gallate) has promising health benefits, particularly in cancer prevention.
• 🔒 Unique Mechanism of Action: EGCG inhibits glutamine enzymes, affecting cellular utilization and the TCA cycle, unlike most natural inhibitors.
• 🏥 Anti-Cancer Properties: EGCG exhibits antiproliferative, anti-angiogenic, and proapoptotic effects in various cancer cell lines and animal models.
• 🚫 Cancer Hallmarks Affected: EGCG impacts genomic instability, resistance to cell death, tumor genesis, carcinogenic activity, and more.
• ⚖️ Metabolic Reprogramming: EGCG suppresses multiple metabolic pathways, including glucose uptake, aerobic glycolysis, and fatty acid metabolism.
• 🧬 Blocking Glycolysis: EGCG blocks PFk enzyme, affecting pyruvate availability and apoptosis by converting fructose-6-phosphate.
• 🔩 Blocking Glutamine Utilization: EGCG inhibits glutamate dehydrogenase, preventing glutamate's conversion to α-ketoglutarate in the TCA cycle.
• 🌟 EGCG as a Powerful Intervention: Cheap, safe, and potentially beneficial, but consult a doctor before adding EGCG to your regimen.