Susan Mooberry, Ph.D., leader of the Experimental Development Therapeutics Program at the University of Texas Health Science Center at San Antonio, has been working to isolate substances in the plant in hopes of finding a new plant-derived cancer drug with the potential of Taxol. Taxol, the first microtubule stabilizer derived from the Yew family, has been an effective chemotherapy drug, but patients eventually develop problems with resistance over time and toxicity at higher doses. Researchers have long been seeking alternatives.
"We've been working with these for years with some good results, but never with the potency of Taxol," said Mooberry, lead author of the study. "Now we have that potency, and we also show for the first time the taccalonolides' cellular binding site."
Microtubules are structures in the cells that act as conveyer belts. They help maintain cell shape and help guide chromosones in cell division to ensure that every new cell, including every new cancer cell, gets a full complement of genetic material. When microtubules are stabilized -- essentially held still so they can't do their jobs -- this disrupts numerous cellular processes, and the cell can die.
The taccalonolides stabilize microtubules in cancer cells, but they do not attack healthy cells, Dr. Mooberry said. "We've run normal prostate cells and normal breast cells through these tests, and they don't die. The taccalonolides selectively kill cancer cells."
Until now, how they did this was unknown. The isolation of these highly potent taccalonolides for the first time by Dr. Mooberry's team shows how they interact directly with microtubules.
Published this month in the Journal of the American Chemical Society.