Month: February 2009

This caught my eye because I’ve been on Velcade before and never gave a second thought to whether or not I should not be consuming green tea/green tea products.

Blood First Edition Paper, prepublished online February 3, 2009; DOI 10.1182/blood-2008-07-171389.

Submitted July 28, 2008
Accepted January 12, 2009

Encouse B. Golden, Philip Y. Lam, Adel Kardosh, Kevin J. Gaffney, Enrique Cadenas, Stan G. Louie, Nicos A. Petasis, Thomas C. Chen, and Axel H. Schonthal*

Department of Pathology, University of Southern California (USC) Keck School of Medicine (KSOM), Los Angeles, CA, United States
Department of Molecular Pharmacology and Toxicology, USC School of Pharmacy (SoP), Los Angeles, CA, United States
Department of Molecular Microbiology and Immunology, USC KSOM, Los Angeles, CA, United States
Department of Chemistry, USC College of Letters, Arts and Sciences, Los Angeles, CA, United States
Department of Clinical Pharmacy and Pharmaceutical Economics and Policy, USC SoP, Los Angeles, CA, United States
Department of Neurosurgery, USC KSOM, Los Angeles, CA, United States

* Corresponding author; email: schontha@usc.edu.

The anticancer potency of green tea and its individual components is being intensely investigated, and some cancer patients already self-medicate with this ‘miracle herb’ in hopes of augmenting the anticancer outcome of their chemotherapy. Bortezomib (Velcade®) is a proteasome inhibitor in clinical use for multiple myeloma. Here, we investigated whether the combination of these compounds would yield increased antitumor efficacy in multiple myeloma and glioblastoma cell lines in vitro and in vivo. Unexpectedly, we discovered that various green tea constituents, in particular (-)-epigallocatechin gallate (EGCG) and other polyphenols with 1,2-benzenediol moieties, effectively prevented tumor cell death induced by bortezomib in vitro and in vivo. This pronounced antagonistic function of EGCG was only evident with boronic acid-based proteasome inhibitors (bortezomib, MG-262, PS-IX), but not with several non-boronic acid proteasome inhibitors (MG-132, PS-I, nelfinavir). EGCG directly reacted with bortezomib and blocked its proteasome inhibitory function; as a consequence, bortezomib could not trigger endoplasmic reticulum stress or caspase-7 activation, and did not induce tumor cell death. Taken together, our results indicate that green tea polyphenols may have the potential to negate the therapeutic efficacy of bortezomib and suggest that consumption of green tea products may be contraindicated during cancer therapy with bortezomib.