Brewing a Potential Cancer Cure

Green tea gets a mixed reputation in scientific circles.

While green tea has reportedly been effective in the treatment or prevention of several cancers, including breast cancer, the findings have been inconsistent and controversial due to lack of quality control and consistency in the commercially available preparations.

Now an interdisciplinary team is making rapid progress in modifying an active component of green tea - a catechin - using benign green chemistry techniques, which make it remarkably effective against breast cancer cells while it doesn't harm normal cells. The key breakthrough is the use of naturally occurring enzymes to "stitch together" green tea catechins - yielding polycatechins that are effective selectively against breast cancer.

Prof. Susan Braunhut of biological sciences, whose lab has been a source of research related to breast cancer for more than a decade, is excited about the collaboration with Physics Prof. Jayant Kumar, director of the Center for Advanced Materials (CAM).

"We've made rapid progress by working together," says Braunhut. "Jayant takes the small molecules, the active component of green tea, and links them together in long strings. This binds them in a much more stable form than is found naturally. The compound is much more potent against cancer cells when compared to the naturally occurring catechins, besides being more stable."

The "long strings" are polymers or oligomers, explains Kumar, "'poly' for many and 'oligo' for a few, depending on the length of the string. We did the synthesis in a one-pot reaction using water, alcohol and the enzyme horseradish peroxidase as a catalyst. There is no component that is toxic, so there are no toxic by-products that have to be removed before being used with living cells." CAM has extensive experience with enzyme-based catalysis. A patent from CAM on enzyme-catalyzed synthesis, in collaboration with Dr. Ashok Cholli, has also been licensed to Polnox for polymeric anti-oxidants.

The green chemistry choice is in striking contrast to some of the best-known anti-cancer drugs such as Taxol(r), which are synthesized in a multi-step process that uses or generates large amounts of carcinogenic chemicals and solvents.

The new polycatechins, tested in vitro in Braunhut's lab, are potent in inhibiting several types of human breast cancer cells. Even more interesting, they are more effective at much lower dosages than naturally occurring catechins. Best of all, the polycatechins do not harm the growth of normal mammary cells when tested in parallel, unlike the other catechins.

"Another great aspect of our compound is that it is ingestible," says Braunhut. "In animal model testing, the mice will be treated with polycatechins in their drinking water. We have several goals. Does the compound work in routine use as a cancer preventive? Does it slow the growth of pre-existing tumors, or cause established large tumors to regress? Can it fully eliminate a tumor?"

As so often happens, the research breakthrough was a tangent from another project - a collaborative research program between the Center for Advanced Materials and the U.S Army Natick Soldier Center (NSC). New compounds were under investigation for use as electrolytes in solar cells, involving Dr. Ferdinando Bruno and Dr. Lynne Samuelson of NSC, with Kumar and Dr. Ramaswamy Nagarajan of CAM. Interested in the potential for medical use, the researchers changed their focus to developing bioavailable versions of the compounds, and turned to Braunhut and her team for their expertise.

The project was funded initially by a Chancellor's seed grant. With preliminary data in hand, the principal investigators were able to submit and win a concept award grant from the U.S. Army Breast Cancer Initiative, Department of Defense, and a student researcher, Subhalakshmi Nagarajan, won a competitive grant from the Environmental Protection Agency (see related story). Also, a patent application has been filed.

"The next question is the bioavailability of the compound in vivo," says Kumar. "The early studies were funded by the Army with a grant of $114,000. The team has also submitted a proposal to the US Army Medical Research and Materiel Command. The competition is enormous; the proposal goes to a board of reviewers that includes breast cancer survivors, so the abstract must be written in accessible form."

Breast cancer is diagnosed in more than 212,000 people in the U.S. each year. The lifetime probability of a woman getting the disease is over 12 percent and, while early detection has helped, there is no cure for breast cancer that has metastasized to bone, brain or liver. Existing chemotherapies are harmful to some of the healthy and normal cells in the body, besides putting a strain on the environment in their manufacture.

Braunhut says, "We believe these new compounds may prove to be a new family of anticancer drugs from green chemistry that will cause a paradigm shift in the development of drugs for breast cancer treatment."