“If what we have seen in animals can be translated to humans, it could be used in conjunction with other drugs to shrink tumors before chemotherapy or surgery.” – Dr. Khosrow Kashfi, City College of New York
The humble aspirin may soon have a new role, say researchers at CCNY. They’ve developed a new compound using classic aspirin as a 'scaffold' that has great promise to be a very potent cancer-fighter - but also safer than the aspirin we know. They recently published findings from two trials - one treating cancer cell cultures and one treating animals with tumors.
The new designer aspirin curbed the growth of 11 different types of human cancer cells in culture…
…(including leukemia and colon, pancreatic, lung, prostate and breast cancer cells) without harming normal cells, according to a report published by ACS Medicinal Chemistry Letters. [See full text here.]
“The key components of this new compound are that it is very, very potent and yet it has minimal toxicity to the cells,” says principal investigator Khosrow Kashfi, PhD, a pharmaceutical biochemist at CCNY.
The aspirin compound also shrank human colon cancer tumors by 85% in live animals…
…again without adverse effects, according to the second paper in Biochemical and Biophysical Research Communications [see before & after photos of mice treated for human colon cancer tumors here]. This paper was published by the CCNY team with colleague Kenneth Olson, PhD, of Indiana University School of Medicine, South Bend.
“If what we have seen in animals can be translated to humans, it could be used in conjunction with other drugs to shrink tumors before chemotherapy or surgery,” says Dr. Kashfi
About NOSH: Two Molecules Increase Aspirin Safety, Potency
Long the go-to drug for minor aches and pains, aspirin and other so-called NSAIDs (non-steroidal anti-inflammatory drugs) such as ibuprofen and naproxen, are known primarily for their ability to calm inflammation. Studies in the 1980’s 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,” notes Dr. 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 (H2S), 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,” Dr. Kashfi says. 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,” Dr. Kashfi adds. “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 H2S. 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, Dr. Kashfi notes.
But any routine working therapy for humans is years away, the next steps being toxicity testing, and then human clinical trials.
Dr. Ravinder Kodela and Dr. Mitali Chattopadhyay are members of Professor Kashfi’s lab at CCNY's Sophie Davis School of Biomedical Education and co-authors on both papers. These studies were funded by The National Cancer Institute through a subcontract from ThermoFisher, and also by the National Science Foundation.
Dr. Kashfi and his colleagues will present these findings at the annual meeting of the American Association for Cancer Research in Chicago, Mar 31 - Apr 4.
Source: Based on City College of New York news release, Mar 8, 2012
1. [Full text.] “NOSH-Aspirin: A Novel Nitric Oxide–Hydrogen Sulfide-Releasing Hybrid: A New Class of Anti-inflammatory Pharmaceuticals,” by Kodela R, Chattopadhyay M, Kashfi K. ACS Medicinal Chemistry Letters, Jan 28, 2012
2. [Scroll down for before & after photos of rats’ tumors.] “NOSH–aspirin (NBS-1120), a novel nitric oxide- and hydrogen sulfide-releasing hybrid is a potent inhibitor of colon cancer cell growth in vitro and in a xenograft mouse model,” by Chattopadhyay M, Kodela R, Olson KR, Kashfi K. Biochemical and Biophysical Research Communications, Feb 16, 2012.