Compound, derived from a rare South American plant, stops the growth of human breast cancer cells

They started with a bare room and an idea. Now, after five years of painstaking, sophisticated tests, scientists at the University of Virginia Health System have discovered that a compound, derived from a rare South American plant, stops the growth of human breast cancer cells in laboratory cultures.

U. Va. Health System scientists Deborah Lannigan and Jeffrey Smith hope that, after further testing, their discovery could translate into a successful drug for the treatment of breast cancer. The disease is the second leading cancer killer of women in the U.S., according to the American Cancer Society, with an estimated 40,410 deaths.

The compound, called SL0101, comes from the plant Forsteronia refracta, a nondescript member of the dogbane family found in the Amazonian rain forest. The compound works like a key in a molecular lock. It inhibits the action of a cancer-linked protein called RSK, which the researchers discovered is important for controlling the growth of breast cancer cells. Interestingly, SL0101 does not alter the growth of normal breast cells. The discovery is detailed in the Feb. 1, 2005 issue of the journal Cancer Research and can be found online at: www.cancerres.aacrjournals.org.

"By preventing RSK from working, we completely stopped the growth of breast cancer cells but did not affect the growth of normal breast cells," said Lannigan, an Assistant Professor of Microbiology at the U. Va. Cancer Center. She compares this discovery to the development of the drug Gleevec for the treatment of chronic myeloid leukemia. Like Gleevec, SL0101 is a signal transduction inhibitor that interferes with the pathways that signal the growth of tumors. "Gleevec is an exciting discovery and we're hoping to have similar success with SL0101," Lannigan said.

For now, Lannigan and Smith have begun testing the compound in animal models. "The next step is to see if SL0101 will prevent the growth of human tumor cells in mice," said Smith, a Research Assistant Professor of Pathology at the U.Va. Cancer Center. "We will modify the structure of SL0101, if necessary, to eventually find a compound that can be carried through to human clinical trials. That's the goal. But human trials will likely be years down the road." The discovery of this potential anti-cancer compound at a U.Va. lab, Lannigan said, also highlights the important role of academic research in drug development.

The researchers collaborated on this discovery with a U.Va. Professor of Chemistry, Dr. Sidney Hecht, who maintains a large number of exotic plants collected by the National Cancer Institute in the 1960's for research purposes. It took years of work to identify and characterize SL0101 as a specific RSK inhibitor. "Finding out that RSK is a good drug target for breast cancer is very exciting," Smith said.

Cancer patients themselves can also take credit for this discovery. A group of volunteers from "Patients and Friends of the U.Va. Cancer Center" provided funds at a crucial stage of the research.