Inhibition of UVB-induced oxidative stress-mediated phosphorylation of mitogen-activated protein kinase signaling pathways in cultured human epidermal keratinocytes by green tea polyphenol (-)-epigallocatechin-3-gallate

Toxicol Appl Pharmacol. 2001 Oct 15;176(2):110-7. doi: 10.1006/taap.2001.9276.


Exposure of normal human epidermal keratinocytes (NHEK) to UVB radiation induces intracellular release of hydrogen peroxide (oxidative stress) and phosphorylation of mitogen-activated protein kinase cell signaling pathways. Here, we demonstrate that pretreatment of NHEK with (-)-epigallocatechin-3-gallate (EGCG), an antioxidant from green tea, inhibits UVB-induced hydrogen peroxide (H(2)O(2)) production and H(2)O(2)-mediated phosphorylation of MAPK signaling pathways. We found that treatment of EGCG (20 microg/ml of media) to NHEK before UVB (30 mJ/cm(2)) exposure inhibited UVB-induced H(2)O(2) production (66-80%) concomitant with the inhibition of UVB-induced phosphorylation of ERK1/2 (57-80%), JNK (53-83%), and p38 (50-77%) proteins. To demonstrate whether UVB-induced phosphorylation of MAPK occurs via UVB-induced H(2)O(2) (oxidative stress) production, NHEK were treated with the oxidant H(2)O(2). Treatment of H(2)O(2) to NHEK resulted in phosphorylation of ERK1/2, JNK, and p38. Using the same in vitro system, when these cells were pretreated with EGCG or with the known antioxidant ascorbic acid (as positive control), H(2)O(2)-induced phosphorylation of ERK1/2, JNK, and p38 was found to be significantly inhibited. These findings demonstrate that EGCG has the potential to inhibit UVB-induced oxidative stress-mediated phosphorylation of MAPK signaling pathways, suggesting that EGCG could be useful in attenuation of oxidative stress-mediated and MAPK-caused skin disorders in humans.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antioxidants / pharmacology*
  • Ascorbic Acid / pharmacology
  • Blotting, Western
  • Catechin / analogs & derivatives*
  • Catechin / pharmacology*
  • Epidermal Cells
  • Epidermis / drug effects
  • Epidermis / metabolism
  • Humans
  • Hydrogen Peroxide / pharmacology
  • JNK Mitogen-Activated Protein Kinases*
  • Keratinocytes / drug effects
  • Keratinocytes / metabolism*
  • MAP Kinase Kinase 4
  • MAP Kinase Signaling System / physiology*
  • MAP Kinase Signaling System / radiation effects*
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinase Kinases / metabolism
  • Mitogen-Activated Protein Kinases / metabolism
  • Oxidants / pharmacology
  • Oxidative Stress / physiology*
  • Oxidative Stress / radiation effects*
  • Phosphorylation
  • Ultraviolet Rays
  • p38 Mitogen-Activated Protein Kinases


  • Antioxidants
  • Oxidants
  • Catechin
  • Hydrogen Peroxide
  • epigallocatechin gallate
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase 4
  • Mitogen-Activated Protein Kinase Kinases
  • Ascorbic Acid