Golden EB, Lam PY, Kardosh A, et al. Green tea polyphenols block the anticancer effects of bortezomib and other boronic acid-based proteasome inhibitors. Blood 2009 Jun 4;113(23):5927-5937.
PMID: 19190249
DOI 10.1182/blood-2008-07-171389
http://bloodjournal.hematologylibrary.org/cgi/content/abstract/113/23/5927
http://bloodjournal.hematologylibrary.org/cgi/content/full/113/23/5927
http://bloodjournal.hematologylibrary.org/cgi/reprint/113/23/5927.pdf
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Blood. 2009 Jun 4;113(23):5927-37. Epub 2009 Feb 3.
Green tea polyphenols block the anticancer effects of bortezomib and other boronic acid-based proteasome inhibitors.
Golden EB, Lam PY, Kardosh A, Gaffney KJ, Cadenas E, Louie SG, Petasis NA, Chen TC, Schönthal AH.
Department of Pathology, University of Southern California Keck School of Medicine, Los Angeles, CA 90089-9094, USA.
Comment in:
Blood. 2009 Jun 4;113(23):5695-6.
Blood. 2009 Jun 11;113(24):6262.
Blood. 2009 Sep 10;114(11):2359-60.
Abstract
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 (BZM) 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 BZM in vitro and in vivo. This pronounced antagonistic function of EGCG was evident only with boronic acid-based proteasome inhibitors (BZM, MG-262, PS-IX), but not with several non-boronic acid proteasome inhibitors (MG-132, PS-I, nelfinavir). EGCG directly reacted with BZM and blocked its proteasome inhibitory function; as a consequence, BZM 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 BZM and suggest that consumption of green tea products may be contraindicated during cancer therapy with BZM.
PMID: 19190249