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Blood, 15 October 2006, Vol. 108, No. 8, pp. 2804-2810. Prepublished online as a Blood First Edition Paper on June 29, 2006; DOI 10.1182/blood-2006-05-022814. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-05-022814v1 108/8/2804    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Shammas, M. A. Articles by Munshi, N. C. Search for Related Content PubMed PubMed Citation Articles by Shammas, M. A. Articles by Munshi, N. C. Related Collections Apoptosis Signal Transduction Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Specific killing of multiple myeloma cells by (-)-epigallocatechin-3-gallate extracted from green tea: biologic activity and therapeutic implications Masood A. Shammas, Paola Neri, Hemanta Koley, Ramesh B. Batchu, Robert C. Bertheau, Vidit Munshi, Rao Prabhala, Mariateresa Fulciniti, Yu tzu Tai, Steven P. Treon, Raj K. Goyal, Kenneth C. Anderson, and Nikhil C. Munshi From the Veterans Administration (VA) Boston Health Care System and Dana Farber Cancer Institute, Harvard Medical School, Boston, MA. Epigallocatechin-3-gallate (EGCG), a polyphenol extracted from green tea, is an antioxidant with chemopreventive and chemotherapeutic actions. Based on its ability to modulate growth factor-mediated cell proliferation, we evaluated its efficacy in multiple myeloma (MM). EGCG induced both dose- and time-dependent growth arrest and subsequent apoptotic cell death in MM cell lines including IL-6-dependent cells and primary patient cells, without significant effect on the growth of peripheral blood mononuclear cells (PBMCs) and normal fibroblasts. Treatment with EGCG also led to significant apoptosis in human myeloma cells grown as tumors in SCID mice. EGCG interacts with the 67-kDa laminin receptor 1 (LR1), which is significantly elevated in myeloma cell lines and patient samples relative to normal PBMCs. RNAi-mediated inhibition of LR1 resulted in abrogation of EGCG-induced apoptosis in myeloma cells, indicating that LR1 plays an important role in mediating EGCG activity in MM while sparing PBMCs. Evaluation of changes in gene expression profile indicates that EGCG treatment activates distinct pathways of growth arrest and apoptosis in MM cells by inducing the expression of death-associated protein kinase 2, the initiators and mediators of death receptor-dependent apoptosis (Fas ligand, Fas, and caspase 4), p53-like proteins (p73, p63), positive regulators of apoptosis and NF-B activation (CARD10, CARD14), and cyclin-dependent kinase inhibitors (p16 and p18). Expression of related genes at the protein level were also confirmed by Western blot analysis. These data demonstrate potent and specific antimyeloma activity of EGCG and provide the rationale for its clinical evaluation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: D. Umeda, S. Yano, K. Yamada, and H. Tachibana Green Tea Polyphenol Epigallocatechin-3-gallate Signaling Pathway through 67-kDa Laminin Receptor J. Biol. Chem., February 8, 2008; 283(6): 3050 - 3058. [Abstract] [Full Text] [PDF]

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