Green tea may counteract anticancer effects of cancer therapy, bortezomib (Velcade)

Feb 3 2009

Green tea products have become regarded as a valuable health supplement, as studies have shown evidence of its benefit against a variety of diseases, including cancer.

However, a new study suggests that some components of green tea may counteract the anticancer effects of one cancer therapy, bortezomib (Velcade), and may be contraindicated for patients taking this medicine to ensure its maximum therapeutic benefit. This study is being prepublished online today in Blood, the official journal of the American Society of Hematology.

Because of its increasing popularity and availability to the public in many formulations, green tea has been increasingly studied to understand its effect on cancer, heart disease, and other conditions. In animal studies, an antioxidant compound in green tea called the EGCG polyphenol (epigallocatechin gallate) has been shown to be a potent anticancer agent, with effects demonstrated against leukemia, as well as lung, prostate, colon, and breast cancer. Among other properties, EGCG binds to a common protein in tumors called GRP78 (which is responsible for preventing cell death) and inhibits its function, thereby assisting in the death of tumor cells.

"We know that cancer patients look to green tea extracts among other natural supplements to complement their therapeutic regimens. We wanted to better understand how the compounds in green tea interact with a cytotoxic chemical therapy and how that may affect patient outcomes," said Axel Schönthal, PhD, of the University of Southern California Keck School of Medicine and senior study author.

In this study, researchers evaluated whether the combination of green tea and bortezomib would improve outcomes against multiple myeloma, a blood cancer, and glioblastoma, a malignant brain tumor. Bortezomib, an anticancer therapy approved to treat multiple myeloma and mantle cell lymphoma, normally fights disease by inhibiting proteasomes and inducing tumor cell death. However, in both in vitro and in vivo mouse experiments, the team was surprised to find that the EGCG compound seemed to prevent bortezomib from fighting the disease by blocking its proteasome inhibitory function - the two compounds effectively contradicted one another in the cell, leaving nearly 100 percent of the tumor cells intact.

Importantly, the team found that EGCG only reacted with proteasome inhibitors that have a boronic acid base (including bortezomib) but did not react with several non-boronic acid-based proteasome inhibitors (such as nelfinavir [Viracept ® ], a treatment for HIV). The researchers determined that the boronic acid in bortezomib helped to bind the EGCG directly to the therapy molecule, thereby cancelling out the effects of both the green tea and the therapy on the tumor cells.

The study findings may have several important implications in the clinical setting. The EGCG blocked bortezomib's antitumor effects at levels that are commonly achieved with the use of available concentrated green tea supplements (as low as 2.5 μM - which can be attained with two to three 250 mg capsules of green tea extract) suggesting the impact is very real for patients supplementing their therapy. The team also believes that as the EGCG inactivates bortezomib's function in the tumor cell, it may also prevent some of the side effects that usually accompany the therapy. As a result, patients taking green tea products to supplement their therapy may experience improved well being and feel encouraged to increase their intake while unknowingly blunting or completely negating the efficacy of their bortezomib treatment.

"Our surprising results indicate that green tea polyphenols may have the potential to negate the therapeutic efficacy of bortezomib," said Dr. Schönthal. "The current evidence is sufficient enough to strongly urge patients undergoing bortezomib therapy to abstain from consuming green tea products, in particular the widely available, highly concentrated green tea and EGCG products that are sold in liquid or capsule form."

The findings of the study are considered specific for patients taking bortezomib as opposed to any other common cancer therapy. The analysis of the study offered a clear understanding of the boronic acid-related mechanisms that cause the negative outcome, offering the conclusion that green tea would counteract most, if not all, compounds that work with boronic acid. However, while there are many chemicals that contain boronic acid, few are being used with patients.

"Although the study has exposed detrimental effects of green tea in specific combination with Velcade, this should not minimize the previously reported potentially beneficial effect of this herb," said Dr. Schönthal. "Related studies with other types of cancer therapies are promising and green tea extract may actually improve the anticancer effects of other drugs."