Could a NOSH-aspirin-a-day keep cancer away?
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 this month in the journal 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 percent 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 the journal Biochemical and Biophysical Research Communications, 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 non-steroidal anti-inflammatory drugs (NSAIDs) 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," noted Professor 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," 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 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. Kashfi noted that any working therapy for humans is years away, but the next step would be toxicity testing, and then clinical trials.
Dr. Ravinder Kodela and Dr. Mitali Chattopadhyay are members of Professor Kashfi's lab at 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.
Professor Kashfi and his colleagues will present these findings at the annual meeting of the American Association for Cancer Research in Chicago, March 31st - April 4th.
More information: Ravinder Kodela, Mitali Chattopadhyay, and Khosrow Kashfi. NOSH-Aspirin: A Novel Nitric OxideHydrogen Sulfide-Releasing Hybrid: A New Class of Anti-inflammatory Pharmaceuticals. Published online ACS Medicinal Chemistry Letters Article ASAP Publication Date (Published online ahead of print January 28, 2012) doi: 10.1021/ml300002m
M. Chattopadhyay et al., NOSHaspirin (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, Biochem. Biophys. Res. Commun. (In press. Available online February 2012), doi:10.1016/j.bbrc.2012.02.051
Provided by City College of New York
- New hybrid 'NOSH aspirin' as possible anti-cancer drug Feb 29, 2012 | not rated yet | 0
- Aspirin may lower the risk of pancreatic cancer Apr 04, 2011 | not rated yet | 0
- Aspirin may cut cancer deaths slightly Jun 07, 2007 | not rated yet | 0
- Long-term use of adult-strength aspirin linked to a moderate decreased cancer risk Apr 18, 2007 | not rated yet | 0
- Aspirin boosts breast cancer survival rate Feb 17, 2010 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
How can there be villous adenoma in colon, if there are no villi there
14 hours ago As title suggest. Thanks :smile:
How can there be a term called "intestinal metaplasia" of stomach
May 21, 2013 Hello everyone, Ok Stomach's normal epithelium is simple columnar, now in intestinal type of adenocarcinoma of stomach it undergoes "intestinal...
Pressure-volume curve: Elastic Recoil Pressure don't make sense
May 18, 2013 From pressure-volume curve of the lung and chest wall (attached photo), I don't understand why would the elastic recoil pressure of the lung is...
If you became brain-dead, would you want them to pull the plug?
May 17, 2013 I'd want the rest of me to stay alive. Sure it's a lousy way to live but it beats being all-the-way dead. Maybe if I make it 20 years they'll...
MRI bill question
May 15, 2013 Dear PFers, The hospital gave us a $12k bill for one MRI (head with contrast). The people I talked to at the hospital tell me that they do not...
Ratio of Hydrogen of Oxygen in Dessicated Animal Protein
May 13, 2013 As an experiment, for the past few months I've been consuming at least one portion of Jell-O or unflavored Knox gelatin per day. I'm 64, in very...
- More from Physics Forums - Medical Sciences
More news stories
(HealthDay)—The American Cancer Society, which is celebrating on Wednesday a century of fighting a disease once viewed as a death sentence, is making a pledge to put itself out of business.
Cancer 4 hours ago | not rated yet | 0
National Lung Screening Trial (NLST) investigators also conclude that the 20 percent reduction in lung cancer mortality with low-dose computed tomography (LDCT) versus chest X-ray (CXR) screening previously reported in the ...
Cancer 5 hours ago | not rated yet | 0
Researchers have developed a new drug delivery system that allows inhalation of chemotherapeutic drugs to help treat lung cancer, and in laboratory and animal tests it appears to reduce the systemic damage ...
Cancer 8 hours ago | not rated yet | 0 |
When turned on, the gene p53 turns off cancer. However, when existing drugs boost p53, only a few tumors die – the rest resist the challenge. A study published in the journal Cell Reports shows how: tumors that live even i ...
Cancer 8 hours ago | not rated yet | 0 |
Study leader, Professor John Mathews from the University of Melbourne said this small increase in cancer risk must be weighed against the undoubted benefits from CT scans in diagnosing and monitoring disease.
Cancer 12 hours ago | not rated yet | 0
Swiss scientists reveal the mechanism responsible for aging hidden deep within mitochondria—and dramatically slow it down in worms by administering antibiotics to the young.
9 hours ago | 4.8 / 5 (5) | 0 |
Researchers from Queen Mary, University of London have led the largest sequencing study of human disease to date, investigating the genetic basis of six autoimmune diseases.
9 hours ago | 4 / 5 (1) | 0 |
Until now, little was scientifically known about the human potential to cultivate compassion—the emotional state of caring for people who are suffering in a way that motivates altruistic behavior.
6 hours ago | 5 / 5 (2) | 2 |
(HealthDay)—Migraines and depression can each cause a great deal of suffering, but new research indicates the combination of the two may be linked to something else entirely—a smaller brain.
5 hours ago | 5 / 5 (1) | 0 |
A new approach for immunizing against influenza elicited a more potent immune response and broader protection than the currently licensed seasonal influenza vaccines when tested in mice and ferrets. The vaccine ...
6 hours ago | not rated yet | 0 |
In a series of lab experiments designed to unravel the workings of a key enzyme widely considered a possible trigger of rheumatoid arthritis, researchers at Johns Hopkins have found that in the most severe ...
8 hours ago | 5 / 5 (1) | 0 |