Inhibition of epidermal growth factor-induced cell transformation by tannins

Masaaki Nomura1, Hirotaka Tsukada, Daisuke Ichimatsu

  • 1Department of Hospital Pharmacy, School of Medicine, Kanazawa University, 13-1 Takara-Machi, Kanazawa, Ishikawa 920-8641, Japan.

Phytochemistry
|September 13, 2005
PubMed

Insights

Certain tannins effectively inhibit tumor promotion in mouse JB6 cells by blocking key signaling pathways. These natural compounds, particularly ellagitannins, show promise as chemopreventive agents by interfering with epidermal growth factor-induced cell transformation.

Area of Science:

  • * Oncology
  • * Pharmacology
  • * Biochemistry

Background:

  • * The JB6 mouse epidermal cell system is a standard model for investigating tumor promotion.
  • * Epidermal growth factor (EGF) is known to induce neoplastic transformation in JB6 Cl 41 cells.
  • * Tannins and triterpenoids are natural compounds with potential anti-cancer properties.

Purpose of the Study:

  • * To evaluate the anti-tumor promoting effects of seven tannins and two triterpenoids.
  • * To investigate the molecular mechanisms by which these compounds inhibit EGF-induced cell transformation.
  • * To identify specific signaling pathways targeted by effective tannins.

Main Methods:

  • * Utilized the JB6 Cl 41 cell line to assess EGF-induced cell transformation.
  • * Tested the inhibitory effects of six tannins (ellagitannins and chromone gallates) and two triterpenoids.
  • * Analyzed the impact of tannins on activator protein 1 (AP-1) and phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathways.
  • * Examined the phosphorylation of extracellular-signal regulated protein kinases and p38 kinases.

Main Results:

  • * Six tannins significantly inhibited EGF-induced cell transformation in a dose-dependent manner without affecting cell growth.
  • * Ellagitannins, but not chromone gallates, attenuated EGF-induced AP-1 activation.
  • * Tannins inhibited EGF-induced activation of the PI3K/Akt pathway, with compounds 3 and 4 suppressing PI3K activation.
  • * Compounds 1 and 3 inhibited EGF-induced phosphorylation of ERK and p38 kinases.

Conclusions:

  • * Tannins, particularly ellagitannins, demonstrate significant anti-tumor promoting activity in the JB6 cell model.
  • * The anti-neoplastic effects are linked to the inhibition of critical signaling pathways, including AP-1 and PI3K/Akt.
  • * These findings suggest that tannins could be valuable chemopreventive agents targeting signal transduction pathways involved in cancer development.