|
|
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 | 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:

|
 |

|
 |
 
Q. Wang, J. Li, J. Gu, B. Huang, Y. Zhao, D. Zheng, Y. Ding, and L. Zeng
Potentiation of (-)-epigallocatechin-3-gallate-induced apoptosis by bortezomib in multiple myeloma cells
Acta Biochim Biophys Sin,
November 10, 2009;
(2009)
gmp094v1.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
P. Lunghi, A. Costanzo, L. Mazzera, V. Rizzoli, M. Levrero, and A. Bonati
The p53 Family Protein p73 Provides New Insights into Cancer Chemosensitivity and Targeting
Clin. Cancer Res.,
November 1, 2009;
15(21):
6495 - 6502.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
E. B. Golden, P. Y. Lam, A. Kardosh, K. J. Gaffney, E. Cadenas, S. G. Louie, N. A. Petasis, T. C. Chen, and A. H. Schonthal
Green tea polyphenols block the anticancer effects of bortezomib and other boronic acid-based proteasome inhibitors
Blood,
June 4, 2009;
113(23):
5927 - 5937.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A.R.M. R. Amin, O. Kucuk, F. R. Khuri, and D. M. Shin
Perspectives for Cancer Prevention With Natural Compounds
J. Clin. Oncol.,
June 1, 2009;
27(16):
2712 - 2725.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. A. Shammas, R. J. Shmookler Reis, H. Koley, R. B. Batchu, C. Li, and N. C. Munshi
Dysfunctional homologous recombination mediates genomic instability and progression in myeloma
Blood,
March 5, 2009;
113(10):
2290 - 2297.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
P. L. Bergsagel and W. M. Kuehl
WSU-WM and BCWM.1 should not be assumed to represent Waldenstrom macroglobulinemia cell lines
Blood,
August 1, 2008;
112(3):
917 - 917.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
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]
|
 |
|
|
|