Inhibition of tetrandrine on epidermal growth factor-induced cell transformation and its signal transduction

Masaaki Nomura1, Rina Yamazaki, Makiko Takaya

  • 1Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, and Hokuriku University, Kanazawa, Japan.

Anticancer Research
|November 1, 2007
PubMed
Abstract

Insights

Tetrandrine, a natural alkaloid, inhibits skin tumor promotion by blocking key signaling pathways. It suppresses epidermal growth factor-induced cell transformation and the activation of transcription factor AP-1 and ERKs.

Area of Science:

  • Oncology
  • Cell Biology
  • Pharmacology

Background:

  • The mouse JB6 epidermal cell system is utilized to investigate tumor promotion mechanisms.
  • Tetrandrine, an alkaloid from Stephania tetrandra S Moore, is examined for its anti-tumor-promoting properties.

Purpose of the Study:

  • To elucidate the mechanism by which tetrandrine exerts its anti-tumor-promoting effect.
  • To investigate tetrandrine's impact on epidermal growth factor (EGF)-induced transformation in JB6 Cl 41 cells.

Main Methods:

  • Assessed tetrandrine's inhibition of EGF-induced JB6 Cl 41 cell transformation in soft agar.
  • Analyzed activator protein-1 (AP-1) activity using an AP-1-dependent reporter assay.
  • Detected phosphorylation of extracellular-signal regulated kinases (ERKs) and Akt via Western blotting.

Main Results:

  • Tetrandrine significantly inhibited EGF-induced cell transformation and AP-1 activation.
  • Tetrandrine suppressed the phosphorylation of ERKs, a key regulator of AP-1.
  • A trend towards suppressed EGF-induced Akt phosphorylation was observed.

Conclusions:

  • Tetrandrine inhibits EGF-induced transformation in JB6 cells.
  • The anti-tumor-promoting effect is mediated by blocking the activation of ERKs, AP-1, and potentially Akt.

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