Green tea effect on Multiple Myeloma cells

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@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.

See also http://myelomic.blogspot.com/2005/12/beneficial-effects-of-green-tea.html