Green tea extract modulates actin remodeling via Rho activity in an in vitro multistep carcinogenic model.
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.
Lu
Qing-Yi
QY
Center for Human Nutrition, University of California at Los Angeles, Los Angeles, CA 90095, USA.
Jin
Yu-Sheng
YS
Pantuck
Allan
A
Zhang
Zuo-Feng
ZF
Heber
David
D
Belldegrun
Arie
A
Brooks
Mai
M
Figlin
Robert
R
Rao
Jianyu
J
D000199:Actins / Q000378:metabolism*; D000611:Aminobiphenyl Compounds / Q000494:pharmacology; D002273:Carcinogens / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects* / Q000378:metabolism; D003572:Cytochalasins / Q000494:pharmacology; D006801:Humans; D008856:Microscopy, Fluorescence; D010936:Plant Extracts / Q000494:pharmacology*; D011108:Polymers / Q000378:metabolism; D022502:Stress Fibers / Q000378:metabolism; D013662:Tea; D020741:rho GTP-Binding Proteins / Q000378:metabolism*
D000199:Actins; D000611:Aminobiphenyl Compounds; D002273:Carcinogens; D003572:Cytochalasins; D010936:Plant Extracts; D011108:Polymers; D013662:Tea; C006757:4-biphenylamine; C007215:cytochalasin E; D020741:rho GTP-Binding Proteins