Tea drinking is a tradition dating back thousands of years and green tea, particularly, is thought to have many health-giving properties. Green tea has also been investigated for possible use in the prevention or treatment of cancer, but a new study by researchers at the University of Southern California has shown that a component of green tea blocks the anti-tumour effect of the proteasome inhibitor, bortezomib (Velcade®), which is used to treat multiple myeloma. Before the study, the researchers believed that epigallocatechin gallate (EGCG), or other components of green tea, would enhance the effectiveness of bortezomib and were surprised to find the opposite effect.
In cell culture experiments, 10µM EGCG provided complete protection from the cytotoxic effects of 10nM bortezomib and 2.5µM EGCG also afforded significant (~80%) protection. In tumours from nude mice implanted subcutaneously with multiple myeloma cells, treatment with bortezomib alone (0.5mg/kg) caused a significant increase in apoptosis. In tumours from mice treated with bortezomib and EGCG (25 or 50mg/kg), however, there was no increase in apoptotic cell death when compared to tumours from untreated control mice.
The authors showed that EGCG was exerting its inhibitory effect on the cytotoxicity of bortezomib by a direct covalent interaction between a 1,2-dihydroxybenzene group of EGCG with the boronic acid group of bortezomib, resulting in the formation of a cyclic boronate ester. EGCG also blocked the cytotoxicity of other boronic acid containing proteasome inhibitors, but had no effect on the cytotoxicity of structurally different proteasome inhibitors.
Because EGCG concentrations of 5-8µM can be achieved by consuming concentrated green tea extracts, the authors strongly advise that cancer patients receiving bortezomib therapy should avoid green tea products, especially the concentrated liquid or capsule forms. Studies show that green tea may improve the effectiveness of other cancer therapies.
The study is published in the February 3rd First Edition of the journal Blood.
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