Rare Plant Compounds from China Undergo Screening at NCI

In July 2008, the United States government signed a research agreement with China to foster collaboration between researchers studying integrative and Traditional Chinese Medicine (TCM) in both countries. One of the first and most promising of these projects is a partnership between the Kunming Institute of Botany (KIB) of China Academy of Sciences and two groups at the National Cancer Institute (NCI).

The Office of Cancer Complementary and Alternative Medicine (OCCAM) began to oversee the growing collaboration after a Memorandum of Understanding (MOU) was signed between KIB and NCI in October 2008. KIB will supply rare and promising specimens, while the Natural Products Branch (NPB) and the Developmental Therapeutics Program (DTP) will screen them in NCI’s system of 60 human cancer cell lines. If any compounds show promise, more drug analysis and development would follow, said Libin Jia, M.D., health scientist administrator at OCCAM.

KIB’s researchers collect and study plant specimens indigenous to their environment, a high-mountain plateau in southwest China that also extends into Tibet. Plants that thrive there could be called “extremophiles,” said David Newman, Ph.D., NPB chief.

Temperatures at these altitudes fluctuate dramatically, with a range in temperatures between the seasons more extreme than in most areas of the world. The climate requires a natural hardiness from plants, because it winnows the supply of possible nutrients. “The ecology is unique, and also remote,” Dr. Newman noted. “We relish the opportunity to study these compounds and extracts, because we really have no idea what we may find.”

Bringing Botanical Compounds Back

Dr. Jia traveled to KIB last fall and returned with seventeen plant-derived compounds, some from plants used in TCM. He delivered the compounds to the DTP labs at NCI’s Frederick, MD, campus where the specimens are now undergoing in vitro screening for anti-cancer activity.

“TCM has already contributed a few compounds, like arsenic trioxide and camptothecin, which are currently used to treat cancer,” explained Dr. Jia. “It would be remarkable if we could find additional ones from the vast number of medicines China has been using for centuries.”

In his recent visit to KIB, Dr. Jia was greeted by KIB Deputy Director Jikai Liu, Ph.D., who provided a tour of the scientific organization. “He showed me their large botanical seed collection (over 1.2 million specimens), which is quite unique,” Dr. Jia recalled. KIB also developed a world-renowned botanical garden, where they cultivate many of the plant species found in the region.

East-West Science and Vice Versa

The millennia-long history of TCM is embodied in the Bencao Gangmu ("Materia Medica”), explained NCI’s Dr. Newman. It is the most complete compendium ever written about TCM, compiled during the Ming Dynasty in the 16th century. “The descriptions of the plants are invariably accompanied by the associated climatic, temporal, and geographic conditions––information on where, when, and how to collect them,” he explained.

“The KIB has an extremely talented group of chemists and plant biologists,” said Dr. Newman, “who have been studying these interactions for years, and who similarly have developed a large collection of plant-associated microbes that may unlock a plant’s medicinal potential.”

Two of the compounds that Dr. Jia brought back from China have already shown promising anti-cancer activity in the KIB labs. The Chinese researchers are hoping that NPB will confirm those findings. But the real collaboration involves putting the rest of the specimens through the rigorous screening process that DTP established around 1990.

Once anti-cancer activity is detected in cells, the work may eventually progress to testing for activity in animal models of cancer. KIB has isolated thousands of compounds, and another batch is on the way to NPB’s labs.

The future of the partnership looks bright, Dr. Jia commented. OCCAM is planning a dialogue among experts on the topic of botanicals in cancer research this summer. KIB’s Dr. Liu will provide NCI researchers with more insight from and details about KIB’s work and resources at that meeting.

Discussions about how the results from some of the projects might eventually be exported back to China are also planned. One of KIB’s goals from the collaboration is to develop a greater capacity to perform its own anti-cancer screening. To facilitate this, Dr. Liu will carry back with him a functional model of the NCI-60 screening cancer cell lines. One day KIB may send scientists to train at NPB and DTP and possibly establish some of the more advanced drug screening methods and technologies, moving science from “west to east.”

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