A simple, well-used pill may provide insight into bowel cancer.
Aspirin, the cost-effective, relatively safe, over-the-counter painkiller, is commonly taken to treat aches and pains.
Also known as acetylsalicylic acid, it is regularly used to prevent more serious conditions, too — such as stroke and blood clots in at-risk patients.
Over the years, evidence has been mounting that aspirin might also prevent bowel (colorectal) cancer.
For instance, a 20-year follow-up of five randomized clinical trials published in 2010 concluded that daily aspirin, taken over many years, "reduced long-term incidence and mortality due to colorectal cancer."
Similarly, in 2010, another study looking at shorter-term aspirin demonstrated "a protective effect against [colorectal cancer] associated with the lowest dose of aspirin [...] after only 5 years use in the general population."
Although evidence is mounting, exactly how aspirin protects against certain cancers is still not understood. In a recent paper, published in the journal Nucleic Acids Research, scientists attempted to find out. They focused on a structure within the cell called the nucleolus.
The nucleolus and aspirin
The nucleolus is the largest structure within the nucleus of cells. Its primary function is to produce ribosomes, which are responsible for synthesizing all of the cell's protein.
When the nucleolus is activated, it appears to drive tumor growth. This seems to be because, as cells divide and proliferate, they need to generate more ribosomes to keep up with increased protein demands — so the nucleolus needs to shift up a gear.
In fact, cancer cells spend the majority of their energy on the production of new ribosomes.
This makes the nucleolus a potential target for cancer researchers. Interestingly, other researchers have noted that nucleolus dysfunction might also play a role in Alzheimer's and Parkinson's diseases.
The scientists involved in the new study, based at the University of Edinburgh's Cancer Research Centre in the United Kingdom, took tumor tissue from colorectal cancer patients and examined aspirin's effects on the cells in the laboratory.
They found that aspirin reduced the activity of a transcription factor called TIF-IA. Without TIF-IA, ribosomes cannot be produced in the nucleolus, thereby limiting the cell's ability to produce protein.
"We are really excited by these findings as they suggest a mechanism by which aspirin may act to prevent multiple diseases," says study co-author Dr. Lesley Stark.
"A better understanding of how aspirin blocks TIF-IA and nucleolar activity provides great promise for the development of new treatments and targeted therapy."
Dr. Lesley Stark
Not every patient who has bowel cancer will respond to aspirin treatment, but understanding why it works at all will help to narrow down which individuals are most likely to benefit.
However, long-term use of aspirin is not recommended for the general population because it can increase the likelihood of internal bleeding.
So, understanding the mechanisms will help scientists to design other cancer drugs that work on the nucleolus or TIF-IA without increasing bleeding risk.