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Cancer Therapy: Preclinical |
1 Center for Human Nutrition and Departments of 2 Pathology and Laboratory Medicine, 3 Urology, 4 Epidemiology, 5 Surgery, and 6 Medicine, University of California at Los Angeles, Los Angeles, California
Request for reprints: JianYu Rao, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California at Los Angeles, Box 951732 Los Angeles, CA 90095-1732. Phone: 310-794-1567; Fax: 310-206-5178; E-mail: jrao{at}mednet.ucla.edu.
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.
Key Words: Green Tea Actin Bladder Cancer
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