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NSF PR 99-01 - January 7, 1999
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Serendipity: Cell Structure Study Uncovers Taxol's
Secrets
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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