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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.
 Previous Article | Next Article 
Submitted May 15, 2006
Accepted June 14, 2006
Specific killing of multiple myeloma cells by (-)-
epigallocatechin-3-gallate extracted from green tea:
biological 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*
VA Boston Health Care System, Harvard Medical School, Dana Farber Cancer Institute, Boston, MA
Dana Farber Cancer Institute, Harvard Medical School, Boston, MA
VA Boston Health Care System, Harvard Medical School, Boston, MA
VA Boston Health Care System, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA
VA Boston Health Care System, Boston, MA
* Corresponding author; email: nikhil_munshi{at}dfci.harvard.edu.
Epigallocatechin-3-gallate (EGCG), a polyphenol
extracted from green tea is an anti-oxidant 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 multiple myeloma cell lines including IL-6
dependent cells and primary patient cells; without
significant effect on the growth of peripheral blood
mononuclear cells (PBMC) and normal fibroblasts.
Treatment with EGCG also led to significant apoptosis in
human myeloma cells grown as tumors in SCID mice. EGCG
interacts with 67Kda laminin receptor 1 (LR1) which is
significantly elevated in myeloma cell lines and patient
samples relative to normal PBMC. 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 PBMC. 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-kappaB activation (CARD10, CARD14), and
cyclin-dependent kinase inhibitors (p16 and p18).
Expression of related genes at protein level were also
confirmed by western blot analysis. These data
demonstrate potent and specific anti-myeloma activity of
EGCG providing the rationale for its clinical evaluation.
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