New Compounds Kill Ovarian, Testicular, Head and
Neck Cancer Cells with Less Toxicity
Platinum-phosphate compounds may be more efficient,
more targeted, have fewer side effects
Nov. 19, 2008 - A new class of compounds called
phosphaplatins can effectively kill ovarian, testicular, head and neck
cancer cells with potentially less toxicity than conventional drugs,
according to a new study published this week in the journal
Proceedings of the National Academy of Sciences.
The compounds could be less harmful than current
cancer treatments on the market such as cisplatin and carboplatin
because they dont penetrate the cell nucleus and attach to DNA, said
lead author Rathindra Bose. Conventional drugs can interfere with the
functions of the cells enzymes, which lead to side effects such as
hearing and hair loss and kidney dysfunction.
Though scientists dont fully understand the
mechanism by which the phosphaplatins kill cancer cells, they suspect
that the compounds bind to the cell surface membrane proteins and
transmit a death signal to the interior of the cell, Bose said.
The compounds are created by attaching platinum to
a phosphate ligand, which can readily anchor to the cell membrane.
Future studies will focus on identifying the exact process.
The findings suggest a paradigm shift in potential
molecular targets for platinum anticancer drugs and in their strategic
development, said Bose, a professor of biomedical sciences and
chemistry and vice president for research at Ohio University who
conducted the work while at Northern Illinois University.
The first drug developed for the treatment of
ovarian and testicular cancers, cisplatin, was approved for use in 1982.
Though its 95 percent effective, it works best during the early stages
of the disease, and some patients develop a resistance to it.
Two drugs introduced later, carboplatin and
oxaliplatin (which is used for colorectal cancer), overcame some of
those problems, but their potency can harm the immune system of
patients, said Bose, who has been studying alternative compounds and
targets for these cancers for 25 years.
Phosphaplatins have the potential to be more
efficient, more targeted and create fewer side effects in the patient,
Bose said. The new study shows that the phosphaplatins can kill ovarian
cells at half of the dosage of conventional drugs, but are just as
potent. Unlike cisplatin, which can decompose quickly and create
additional toxic side effects through the decomposition products, the
new compounds show no signs of degradation after seven days, he added.
A U.S. patent is pending on the work; two
provisional patents have been filed. Bose and his colleagues next will
test the compounds in mice models.
Co-authors of the study are Leila Maurmann of
Kansas State University, and Robert Mishur, Linda Yasui, Shefalika
Gupta, W. Scott Grayburn, Heike Hofstetter and Tara Milton, all of
Northern Illinois University.
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