Jan. 11, 1999 Scientists funded by the National Science Foundation (NSF) have learned exactly how the anti-cancer drug Taxol kills tumor cells. Their new insight into Taxol, happened upon during a study of molecular structures related to cell division, may aid researchers in developing more advanced cancer-fighting drugs.
Biophysicist Lee Makowski of Florida State University (FSU), in collaboration with researchers led by Bonnie Wallace of the University of London's Birkbeck College, published his findings on Taxol in the January 8th issue of the Journal of Molecular Biology.
Makowski and his research group at FSU were studying the structure of microtubules, the molecular cables that pull two cells apart during cell division, when their research led them to examine how Taxol triggers apoptosis, a natural mechanism that kills malfunctioning cells as part of the body's defense against cancer.
For more 25 years, researchers have known that Taxol targets microtubules and prevents cells from dividing, which then triggers apoptosis, a cellular mechanism also referred to as programmed cell death. Makowski's group, however, found that Taxol also attacks a second target in cancer cells -- one that may make it easier for researchers to develop more efficient anti-cancer drugs.
In order to find which other parts of a cell Taxol could bind, the Florida State researchers created a huge library of bacterial viruses, each genetically engineered to exhibit a fragment of a different cellular protein. They then screened the library to find which bacterial viruses bind to Taxol.
In addition to microtubules, they found that Taxol also binds to a protein called Bcl-2, a molecule first discovered in human B-cell leukemias. Bcl-2 is an important component in the mechanisms that cause apoptosis, acting as a safeguard to block the cell from completing the process of cell death. By attaching to Bcl-2, Taxol stops the protein from working and allows apoptosis to continue.
"It's a two-pronged attack against cancer cells," said Makowski, currently an NSF program manager in the division of biological infrastructure. "Taxol keeps cells from dividing, which halts cell growth, but then it also binds to molecules of the Bcl-2 protein, which causes cell death."
As effective as Taxol is against certain types of cancer, researchers need to know more about how it works in order to improve it.
"Using these complicated, yet elegant laboratory techniques, we've provided a model through which researchers can imitate protein targets in the human body. Researchers can then refine drugs more easily, leading to more effective therapies with fewer side effects," said Makowski.
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