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Science & the Public

Cancer fighting green tea may have a dark side

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For more than a decade, study after study has extolled the cancer-fighting virtues of green tea, or at least extracts of its polyphenol antioxidants. But preliminary data now suggest that for some people this herbal remedy may not prove beneficial — or even benign. In test-tube experiments on cancer cells and in animals, green tea’s polyphenols inactivated the cell-killing activity of a drug used to treat blood cancers.

Physicians prescribe bortezomib, a drug sold under the trade name Velcade, to patients with multiple myeloma. This treatable, though incurable, cancer begins in antibody-producing white blood cells. As the abnormal cells replicate and build within bone marrow, they risk damaging the bone itself. Once this disease spreads to marrow-producing tissue at several sites in the body, it’s termed multiple myeloma. Infections, liver failure and death can result.

Bortezomib is also approved for treatment of mantle cell lymphoma, a rare and hard-to-cure form of non-Hodgkin's disease.

Buoyed by all of the benefits ascribed to green-tea polyphenols — particularly (-)-epigallocatechin gallate, better known as EGCG — a Los Angeles-based team of researchers decided to treat multiple myeloma with bortezomib in combination with various green-tea polyphenols, especially EGCG. The pharmacologists had anticipated the drug-tea duo would dramatically outperform use of bortezomib alone. In fact, the pairing totally shut down the drug’s anticancer activity.

The findings appear in Blood, a journal of the American Society of Hematology, which published the new green-tea paper early online, this week, ahead of print.

That EGCG “blocked the therapeutic action of Velcade was completely unexpected,” according to team leader Axel H. Schönthal of the University of Southern California School of Medicine.

As a so-called proteasome inhibitor, bortezomib deactivates proteasomes —large protein complexes that help destroy cellular proteins that have outlived their usefulness. In the test-tube and in mice, EGCG and its polyphenolic kin blocked the cancer drug’s proteasome inhibition. A key constitutent of the drug is boron. And that’s proved interesting, Schönthal’s team notes, because they observed no green-tea inactivation of cancer-fighting proteasome inhibitors that lack boron.

Other dietary constituents — most notably vitamin C and iron — can also poison the activity of bortezomib, but only at concentrations 100-fold higher than EGCG requires. In fact, EGCG concentrations needed to turn off the drug’s anticancer activity in the latest study “can easily be achieved [in people] after the ingestion of capsules containing green-tea extract,” Schönthal and his colleagues report. “We therefore have no doubt that our discovery is highly relevant for clinical considerations.”

“The most immediate conclusion,” Schönthal says, is that “patients undergoing cancer therapy with Velcade must avoid green tea, and in particular all of its concentrated [polyphenol extracts]" that are so readily available in health-food stores and online.

Adding to Schönthal’s concerns: Green-tea supplements may provide symptomatic relief for some patients treated with bortezomib — precisely because the tea constituents are turning off the cell-poisoning activity responsible for triggering side effects.

But don’t look for a simple message in this research, such as that green tea is bad for chemotherapy patients. In a separate study using another “well-established chemotherapeutic drug” — one that Schönthal won’t yet name — “inclusion of EGCG appears to yield an ‘encouragingly beneficial’ outcome.”

The Multiple Myeloma Research Foundation provided funding for the new study.

Citations

Golden, E.B. and . . . A.H. Schönthal. 2009. Green Tea Polyphenols Block the Anticancer Effects of Bortezomib and Other Boronic Acid-Based Proteasome Inhibitors. Blood(in press). DOI 10.1182/blood-2008-08-174300
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