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Molecular Biology and Genetics

Inhibition of Tumor Promoter-induced Activator Protein 1 Activation and Cell Transformation by Tea Polyphenols, (-)-Epigallocatechin Gallate, and Theaflavins

Zigang Dong, Wei-ya Ma, Chuanshu Huang and Chung S. Yang
Zigang Dong
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Wei-ya Ma
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Chuanshu Huang
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Chung S. Yang
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DOI:  Published October 1997
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Abstract

(-)-Epigallocatechin gallate (EGCG) and theaflavins are believed to be key active components in tea for the chemoprevention against cancer. However, the molecular mechanisms by which EGCG and theaflavins block carcinogenesis are not clear. We have used the JB6 mouse epidermal cell line, a system that has been used extensively as an in vitro model for tumor promotion studies, to examine the anti-tumor promotion effects of EGCG and theaflavins at the molecular level. EGCG and theaflavins inhibited epidermal growth factor- or 12-O-tetradecanoylphorbol-13-acetate-induced cell transformation in a dose-dependent manner. At the dose range (5–20 µm) that inhibited cell transformation, EGCG and theaflavins also inhibited AP-1-dependent transcriptional activity and DNA binding activity. The inhibition of AP-1 activation occurs through the inhibition of a c-Jun NH2-terminal kinase-dependent, but not an extracellular signal-regulated protein kinase (Erk) 1-dependent or Erk2-dependent, pathway. Because the transcription factor AP-1 is important for tumor promoter-induced neoplastic transformation, the inhibitory effects on AP-1 activation by EGCG and theaflavins may further explain the anti-tumor promotion action of these tea constituents.

Footnotes

  • ↵1 This research was supported by the Hormel Foundation and NIH Grant CA56673.

  • ↵2 To whom requests for reprints should be addressed, at The Hormel Institute, University of Minnesota, 801 16th Ave NE, Austin, MN 55912. Phone: (507) 437-9640; Fax: (507) 437-9606; E-mail: zgdong@wolf.co.net.

  • Received April 30, 1997.
  • Accepted July 30, 1997.
  • ©1997 American Association for Cancer Research.
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October 1997
Volume 57, Issue 19
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Inhibition of Tumor Promoter-induced Activator Protein 1 Activation and Cell Transformation by Tea Polyphenols, (-)-Epigallocatechin Gallate, and Theaflavins
Zigang Dong, Wei-ya Ma, Chuanshu Huang and Chung S. Yang
Cancer Res October 1 1997 (57) (19) 4414-4419;

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Inhibition of Tumor Promoter-induced Activator Protein 1 Activation and Cell Transformation by Tea Polyphenols, (-)-Epigallocatechin Gallate, and Theaflavins
Zigang Dong, Wei-ya Ma, Chuanshu Huang and Chung S. Yang
Cancer Res October 1 1997 (57) (19) 4414-4419;
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