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

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.

• Authors: Qing-Yi Lu, Yu-Sheng Jin, Allan Pantuck, Zuo-Feng Zhang, David Heber, Arie Belldegrun, Mai Brooks, Robert Figlin, Jianyu Rao
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 11 Issue 4 Pg. 1675-83 (Feb 15 2005) ISSN: 1078-0432 [Print] United States
• PMID: 15746073 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, P.H.S.)

Chemical References

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

Topics

• 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, metabolism)
• Cytochalasins (pharmacology)
• Humans
• Microscopy, Fluorescence
• Plant Extracts (pharmacology)
• Polymers (metabolism)
• Stress Fibers (metabolism)
• Tea
• rho GTP-Binding Proteins (metabolism)