Green tea extract modulates actin remodeling via Rho activity in an in vitro multistep carcinogenic model

Clin Cancer Res. 2005 Feb 15;11(4):1675-83. doi: 10.1158/1078-0432.CCR-04-1608.

Abstract

Alteration of actin polymerization and loss of actin filaments is a marker of cellular dedifferentiation and early malignant transformation. To study this phenomenon, an in vitro human urothelial model consisting of two cell lines, HUC-PC and MC-T11, were incorporated into the study design. These two cell lines have different malignant transformation potential. The effect of green tea extract (GTE), a potential anticancer agent, on actin remodeling was investigated. Upon exposure to the carcinogen 4-aminobiphenyl (4-ABP), the untransformed HUC-PC undergoes malignant transformation whereas the transformed MC-T11 progresses from noninvasive to invasive tumor. GTE induces actin polymerization in MC-T11 cells in a dose-responsive manner, but this effect is less obvious in the untransformed, more differentiated HUC-PC cells, which natively have higher actin polymerization status. In contrast, GTE antagonizes carcinogen 4-ABP induced actin depolymerization and stress fiber disruption in HUC-PC cells. In MC-T11 cells, GTE inhibits 4-ABP induced motility by increasing cell adhesion and focal adhesion complex formation. The effect of GTE on actin remodeling seems to be mediated by the stimulation of small GTP-binding protein Rho activity, because C3 exoenzyme, a specific inhibitor for Rho, blocks GTE-mediated Rho activation and stress fiber formation in MC-T11 cells. This study shows that GTE exerts an effect on cytoskeletal actin remodeling and provides further support for the use of GTE as a chemopreventive agent.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Actins / metabolism*
  • Aminobiphenyl Compounds / pharmacology
  • Carcinogens / pharmacology
  • Cell Adhesion / drug effects
  • Cell Line
  • Cell Line, Transformed
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Transformation, Neoplastic / drug effects*
  • Cell Transformation, Neoplastic / metabolism
  • Cytochalasins / pharmacology
  • Humans
  • Microscopy, Fluorescence
  • Plant Extracts / pharmacology*
  • Polymers / metabolism
  • Stress Fibers / metabolism
  • Tea*
  • rho GTP-Binding Proteins / metabolism*

Substances

  • Actins
  • Aminobiphenyl Compounds
  • Carcinogens
  • Cytochalasins
  • Plant Extracts
  • Polymers
  • Tea
  • 4-biphenylamine
  • cytochalasin E
  • rho GTP-Binding Proteins