NOSH-aspirin: The scaffold of aspirin (red) bears arms that produce nitric acid (NO, purple) and hydrogen sulfide (H2S, yellow), which boost the safety and potency of the cancer-fighter. Image: The City College of New York |
The
humble aspirin may soon have a new role. Scientists from The City College of
New York have developed a new aspirin compound that has great promise to be not
only an extremely potent cancer fighter, but even safer than the classic medicine
cabinet staple.
The
new designer aspirin curbed the growth of 11 different types of human cancer
cells in culture without harming normal cells, reported a team from the Sophie
Davis School of Biomedical Education of The City College of New York in a paper
published in ACS Medicinal Chemistry
Letters. The cancers controlled included colon, pancreatic, lung, prostate,
breast, and leukemia. “The key components of this new compound are that it is
very, very potent and yet it has minimal toxicity to the cells,” said associate
professor Khosrow Kashfi, the principal investigator.
The
aspirin compound also shrank human colon cancer tumors by 85% in live animals,
again without adverse effects, according to a second paper in press by the City College
researchers and colleague Kenneth Olson of Indiana University School of
Medicine, South Bend.
Their results will appear in Biochemical
and Biophysical Research Communications, is now available online. “If what
we have seen in animals can be translated to humans,” said Professor Kashfi, “it could be used in conjunction with other drugs to shrink tumors before
chemotherapy or surgery.”
Long
the go-to drug for minor aches and pains, aspirin and other so-called nonsteroidal
antiinflammatory drugs (NSAIDs) such as ibuprofen and naproxen, are known
primarily for their ability to calm inflammation. Studies in the 1980s resolved
a decades-old debate on the utility of a daily dose of aspirin to cut the risk
of heart attack and stroke.
More
recent studies tracking regular use of the drug and other NSAIDs demonstrated
their remarkable ability to inhibit the growth of cancer. “There’s a lot of
data on aspirin showing that when taken on a regular basis, on average it
reduces the risk of development of colon cancer by about 50% compared to
nonusers,” noted Kashfi.
The
fly in the ointment has been that prolonged use of aspirin posed its own
dangers: Side effects ranging from bleeding ulcers to kidney failure. To
resolve this, the researchers created a hybrid of two earlier formulations,
which they have called “NOSH-aspirin.” They used the aspirin as a scaffold to
support two molecules that have been shown to increase the drug’s safety and
potency.
One
arm of the hybrid aspirin releases nitric oxide (NO), which helps protect the
stomach lining. The other releases hydrogen sulfide, which the researchers have
previously shown enhances aspirin’s cancer-fighting ability. The researchers
suspected that the hybrid would be more effective than either of the two
components alone to boost aspirin’s safety and power against cancer.
“The
hybrid is more potent—and it is more potent by orders of magnitude—compared to
aspirin,” said Kashfi. Only 24 hours after treating a culture of cancer cells,
the NOSH-aspirin demonstrated 100,000 times greater potency than aspirin alone. “At 72 hours it is about 250,000 times more potent in an in vitro cell culture against human colon cancer,” Kashfi added. “So you need a lower amount to get the same result.”
The
effect of the hybrid was also far greater than the sum of its parts. Its
potency was as much as 15,000 times greater than existing NO-aspirins and
80-fold more than those that incorporate hydrogen sulfide. The upshot is that a
drug based on this hybrid would require lower doses to be effective, minimizing
or potentially eliminating its side effects.
In
the second study, when mice bearing human colon cancer tumors on their flanks
were given oral NOSH-aspirin, the compound caused cancer cells to self-destruct,
inhibited the proliferation of the cells and significantly reduced tumor growth
without any signs of toxicity in the mice.
The
stage is set for the development of a drug based on NOSH-aspirin. Kashfi noted
that any working therapy for humans is years away, but the next step would be
toxicity testing, and then clinical trials.
Filed Under: Drug Discovery
