| Paw-Paw's Promising Proteins
By Sean Henahan, Access Excellence
 Las
Vegas, NEV. (9/12/97)- Proteins found in the bark of the Paw Paw tree
appear to possess potent anti-cancer properties, particularly against cancers
resistant to existing therapies, reported researchers at the American Chemical
Society national meeting.
The pawpaw tree (Asimina triloba), also known as the Hoosier
banana, bears the largest fruit native to North America. Researchers from
Purdue University report preliminary data from cultured cell studies that
compounds isolated from the bark of the tree are effective tumor killing
agents.
One way that cancer cells resist the effects of toxic anticancer drugs
is by pumping the agents out of the cell before it can take effect. These
pumps are called P-glycoprotein mediated pumps and are named for the type
of protein used to construct and operate them. While not all cancer cells
have these pumps, those that do can resist treatment and multiply, explained
Jerry L. McLaughlin, Department of Medicinal Chemistry and Molecular Pharmacology,
School of Pharmacy and Pharmaceutical Sciences, Purdue University.
"Multidrug-resistant cancer is hard to treat because the cancer cell
has developed a mechanism to get around the anti-cancer agent," says McLaughlin.
"Tumor cells that survive chemotherapy treatments often recover with increased
resistance to the agent used in the original treatment program as well
as to other related drugs."
McLaughlin and colleagues have identified more than 40 pawpaw compounds
with anti-cancer properties. Of these, a series of the compounds, called
Annonaceous acetogenins, have the remarkable ability to kill resistant
cancer cells that employ P-glycoprotein mediated pumps.
The researchers designed a laboratory study to analyze the cytotoxic
or cell-killing effects of one of the compounds, called bullatacin, on
human mammary cancer cells. The study compared bullatacin's effects on
standard, nonresistant cancer cells and on multidrug-resistant cells. Bullatacin
preferentially killed the multidrug-resistant cells by inhibiting the production
of adenosine triphosphate.
"A multidrug-resistant cell requires a tremendous amount of energy to
run the pump and extrude things out of the cell," McLaughlin says. "By
inhibiting ATP production, we're essentially pulling the plug on its energy
source."
Though the pawpaw compounds also inhibited ATP production in noncancerous
cells and nonresistant cancer cells, those cells were not affected as dramatically,
McLaughlin says.
"Normal cells and standard cancer cells may be able to minimize the
effects of this compound because they don't require the vast amounts of
energy needed by the pump-running cells," McLaughlin says. "The resistant
cell is using its extra energy for this pump as well as to grow, so it
is really taxed for energy. When we mess with the energy supply, it kills
the cell."
If proven effective in animals and humans, McLaughlin says, the compounds
may be used to treat multidrug resistance in a variety of cancers, because
many types of cancer cells develop resistance by employing a pump.
The findings, reported at this year's meeting of the American Chemical
Society, were published this summer in the journal Cancer Letters and the
Journal of Medicinal Chemistry.
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