Green tea polyphenols block the anticancer effects of bortezomib and other boronic acid-based proteasome inhibitors
- PMID: 19190249
- DOI: 10.1182/blood-2008-07-171389
Green tea polyphenols block the anticancer effects of bortezomib and other boronic acid-based proteasome inhibitors
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.
Comment in
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Bortezomib and EGCG: no green tea for you?Blood. 2009 Jun 4;113(23):5695-6. doi: 10.1182/blood-2009-03-204776. Blood. 2009. PMID: 19498025 Free PMC article.
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From orbital hybridization to chemotherapeutics neutralization.Blood. 2009 Jun 11;113(24):6262. doi: 10.1182/blood-2009-03-209148. Blood. 2009. PMID: 19520822 No abstract available.
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Therapeutic use of tea derivatives: all that glitters is not gold.Blood. 2009 Sep 10;114(11):2359-60. doi: 10.1182/blood-2009-07-231761. Blood. 2009. PMID: 19745081 No abstract available.
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