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Related Experiment Videos

The antifolate activity of tea catechins.

Enma Navarro-Perán1, Juan Cabezas-Herrera, Francisco García-Cánovas

  • 1Grupo de Investigación de Enzimología, Departamento de Bioquímica y Biología Molecular A, Facultad de Biología, Universidad de Murcia, Spain.

Cancer Research
|March 23, 2005
PubMed
Summary

(-)-Epigallocatechin gallate (EGCG) from green tea inhibits dihydrofolate reductase (DHFR). This explains green tea’s cancer-preventive effects and traditional medicinal uses by targeting cell growth and apoptosis.

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Area of Science:

  • Biochemistry
  • Molecular Biology
  • Pharmacology

Background:

  • (-)-Epigallocatechin gallate (EGCG), a polyphenol from green tea, is present in serum and tissues of green tea drinkers.
  • Epidemiologic studies suggest green tea consumption has prophylactic effects against certain cancers.
  • Tea extracts are traditionally used in alternative medicine for anticarcinogenic and antibiotic purposes.

Purpose of the Study:

  • To investigate the inhibitory effect of EGCG on dihydrofolate reductase (DHFR) activity.
  • To provide evidence for EGCG's role in the cancer-preventive effects of green tea.
  • To explore the mechanism of action of EGCG in cancer cells.

Main Methods:

  • In vitro enzyme inhibition assays with bovine and chicken liver DHFR.

Related Experiment Videos

  • Structural modeling of EGCG binding to human DHFR.
  • Cell cycle analysis and apoptosis induction studies in lymphoma cells.
  • Sensitivity assays with antifolates and EGCG under folate-depleted conditions.

    • Main Results:

    • EGCG acts as a slow, tight-binding inhibitor of bovine liver DHFR (K(I) = 0.109 micromol/L) and a competitive inhibitor of chicken liver DHFR (K(I) = 10.3 micromol/L).
    • Structural modeling indicates EGCG binds to the active site of human DHFR.
    • EGCG inhibits lymphoma cell growth (IC50 = 20 micromol/L), arrests the cell cycle at G0-G1, and induces apoptosis.
    • Folate depletion enhances sensitivity to EGCG and antifolates, confirming DHFR as the target.

    Conclusions:

    • EGCG is a potent inhibitor of DHFR at concentrations achievable through green tea consumption.
    • EGCG's inhibition of DHFR likely contributes to the observed cancer-preventive effects of green tea.
    • EGCG exhibits anticancer properties through cell cycle arrest and apoptosis induction, validating its traditional medicinal use.