Aspirin for All? From Fighting Cardiovascular Disease to Cancer and Beyond
Aspirin is an anti-platelet, analgesic and anti inflammatory drug, most popularly used as an over-the-counter medication for fever, pain and inflammation. ‘An aspirin a day’ has long been the general wisdom of cardiologists, for its anti-thrombotic effects protect against heart attack and non-hemorrhagic stroke.
However, recent research efforts have shown that the full potential benefits of the little white pill go far beyond what was previously known.
As an analgesic, aspirin is used almost interchangeably alongside paracetamol. However, by virtue of its anti inflammatory properties, it makes for a superior option in relieving arthritic and low back pain situations where paracetamol is ineffective, this action occurs by irreversibly inhibiting an enzyme called cycloxygenase-1 (COX-1), reducing production of pro-inflammatory mediators, namely prostaglandins.
Equally well established as its anti inflammatory role, and perhaps more clinically important is the use of aspirin in primary and secondary prevention of cardiovascular events.
Daily low dose aspirin therapy is recommended for patients who are at identified risk of thrombotic events including myocardial infarction and stroke. Inhibition of platelet aggregation is due to a decrease in thromboxane A2 (TXA-2), an extension of the same mechanism of action described before.
Cancer Prevention and Immunotherapy
In what looks to be a promising bit of research, scientists have investigated the negative relationship between aspirin use and cancer risk. In analysis of long-term epidemiologic population wide studies, Harvard researchers have shown that regular aspirin use significantly reduces risk of developing gastrointestinal cancers, like colorectal, esophageal and stomach cancer.
In participants who took a low dose aspirin tablet at least twice a week over 5-6 years, the risk of colorectal cancer was slashed by 19%, while the risk of any type of GIT cancer fell by 15%. When extended to risk of any type of cancer, regular aspirin use lowers the odds by 3%.
This protective effect of aspirin certainly complements the benefit of endoscopic screening, and the research team encourages prescription of low dose aspirin to patients who have risk factors like a family history of colorectal cancer.
And it doesn’t end there. Cancer research UK and the National Institute for Health Research, UK have been funding ongoing trials combining cancer immunotherapy with aspirin. It has been found that several types of cancers produce large amounts of prostaglandin E2, and this molecule aids cancer cells to evade the host immune system.
Aspirin, by blocking production of PGE2, brings cancer cells back under the radar of the immune system, thereby greatly potentiating the effect of existing immunotherapeutic drugs.
The results of experiments conducted on mice, published in the journal Cell, have been encouraging, spurring the ‘Add Aspirin’ trial, which aims to study definitely how aspirin might benefit human cancer patients.
Potential in Inflammatory and Neurodegenerative Diseases:
Much of the credit for aspirin’s role in curbing inflammation may go to its key active ingredient, salicylic acid. In 2015, researchers at Boyce Thomson Institute undertook an effort to identify potential molecular targets of salicylic acid; two of which emerged as particularly significant: HMGB1 and GAPDH.
HMGB1 enters the bloodstream when cancerous cells are present or when tissue damage occurs, and stimulates cytokine production by immune cells, setting an inflammatory response into motion.
HMGB1 is associated with a number of inflammatory diseases, such as rheumatoid arthritis, systemic lupus erythematosus (both autoimmune) and certain cancers. Salicylic acid blocks the activities of HMGB1, halting major inflammatory pathways right in their tracks.
The other protein, GAPDH, has as one of its auxiliary functions, the job of swooping down upon cells that have undergone oxidative stress and inducing cell death in them.
This mechanism is meant to remove cells that are damaged beyond repair, and is also responsible for the massive neuronal death seen in neurodegenerative diseases, notably Alzheimer’s, Parkinson’s and Huntington’s diseases. Again, salicylic acid has been discovered to bind to this target protein and block its activity.
Scientists are optimistic that therapeutic developments will keep pace with the strides made in molecular research. In fact, two derivatives of salicylic acid – that are much more potent than aspirin – have been identified already, leading one to think that aspirin-like drugs could soon be used as a wide-ranging treatment option.
While daily low-dose aspirin intake is widely being promoted in the older population group to strategically kill two (several) birds in one stone, it must be remembered to consult your personal physician in any case, for potential risks and relative benefit of all drugs vary from patient to patient.
Cao Y, Nishihara R, Wu K, et al. Population-wide Impact of Long-term Use of Aspirin and the Risk for Cancer. JAMA Oncol. Published online March 03, 2016. doi:10.1001/jamaoncol.2015.6396
Cancer Research UK. “Aspirin could hold key to supercharged cancer immunotherapy.” ScienceDaily. ScienceDaily, 3 September 2015. .
Choi HW, Tian M, Manohar M, Harraz MM, Park S-W, Schroeder FC, et al. (2015) Human GAPDH Is a Target of Aspirin’s Primary Metabolite Salicylic Acid and Its Derivatives. PLoS ONE 10(11): e0143447. doi:10.1371/journal.pone.0143447
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