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http://dx.doi.org/10.5352/JLS.2009.19.9.1200

Anti-invasive Activity of Human Breast Carcinoma Cells by Genistein through Modulation of Tight Junction Function  

Kim, Sung-Ok (Department of Biomaterial Control (BK21 program), Graduate School, Dongeui University College of Oriental Medicine)
Jeang, Yang-Kee (Department of Biotechnology, College of Natural Resources and Life Science and BK21 Center for Silver-Bio Industrialization, Dong-A University)
Choi, Yung-Hyun (Department of Biomaterial Control (BK21 program), Graduate School, Dongeui University College of Oriental Medicine)
Publication Information
Journal of Life Science / v.19, no.9, 2009 , pp. 1200-1208 More about this Journal
Abstract
Tight junctions (TJs) that act as paracellular permeability barriers play an essential role in regulating the diffusion of fluid, electrolytes and macromolecules through the paracellular pathway. In this study, we investigated the correlation between the tightening of TJs, permeability and the invasive activity of genistein - a bioactive isoflavone of soybeans - in human breast carcinoma MCF-7 and MDA-MB-231 cells. The inhibitory effects of genistein on cell proliferation, motility and invasiveness were found to be associated with the increased tightness of the TJs, which was demonstrated by an increase in transepithelial electrical resistance and a decrease in paracellular permeability. Additionally, the immunoblotting results indicated that genistein repressed the levels of the proteins that comprise the major components of TJ, claudin-3 and claudin-4, which play a key role in the control and selectivity of paracellular transport. Furthermore, genistein decreased the metastasis-related gene expressions of insulin like growth factor-1 receptor and snail, while concurrently increasing that of thrombospondin-1 and E-cadherin. In addition, we demonstrated that claudins play an important role in the anti-motility and invasiveness of genistein using claudin-3 small interfering RNA. Taken together, our results indicate a possible role for genistein as an inhibitor of cancer cell invasion through the tightening of TJs, which may counteract the up-regulation of claudins. In addition, our results indicate that this may be beneficial for the inhibition of tumor metastasis.
Keywords
Genistein; tight junction; claudin; invasion;
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