Saccharin is commonly found in sugar-free products used to sweeten hot beverages. In the future, will it be found in anticancer drugs?
Saccharin is utilized as a sweetener in many sugar-free products, and now researchers are proposing that it could be used as a key ingredient in new drugs for treating aggressive cancers with fewer side effects.
"It never ceases to amaze me how a simple molecule, such as saccharin - something many people put in their coffee every day - may have untapped uses, including as a possible lead compound to target aggressive cancers," says study author Robert McKenna, PhD, from the University of Florida.
The findings of McKenna and his colleagues are being presented today at the 249th National Meeting & Exposition of the American Chemical Society (ACS).
Saccharin's potential use in the development of new anticancer drugs is due to the way in which it binds to and deactivates a protein called carbonic anhydrase IX. This protein is found in some aggressive cancers and plays a role in the proliferation of these cancers in the brain, breast, kidneys, liver, lungs and pancreas.
Due to the way in which saccharin interacts with carbonic anhydrase IX, the researchers want to use it as a base for drugs that could restrict the growth of cancer and make cancerous cells potentially more vulnerable to other therapies such as chemotherapy and radiation treatment.
Carbonic anhydrase IX regulates the pH of cancer cells and their surroundings, maintaining levels of acidity that are optimum for the growth and spread of cancer to other parts of the body. As carbonic anhydrase IX is not typically found in most healthy human cells, McKenna states that it is a prime target for anticancer drugs.
Saccharin inhibits carbonic anhydrase IX but not other vital proteins
Unfortunately, carbonic anhydrase IX is similar to other proteins in the body - other forms of carbonic anhydrase that are required for the healthy functioning of the body. The problem researchers faced was how to develop a substance to block carbonic anhydrase IX that did not affect similar proteins needed by the body.
A group of scientists from the University of Florence, Italy, discovered a potential solution to this problem. They found that saccharin inhibits carbonic anhydrase IX but does not affect the other similar proteins that are required to keep the body healthy.
Another team from Griffith University, Australia, took this work further by creating a compound in which a glucose molecule is chemically linked to saccharin. The compound reduced the amount of saccharin needed to inhibit carbonic anhydrase IX and was 1,000 times more likely to bind to the protein than saccharin alone.
McKenna and his team have now used X-ray crystallography - a method of examining atomic and molecular structures - to determine precisely how saccharin binds to carbonic anhydrase IX. The researchers have also investigated the ways in which saccharin or saccharin-based compounds might be altered to improve their binding capabilities and anticancer potential.
"This result opens up the potential to develop a novel anticancer drug that is derived from a common condiment that could have a lasting impact on treating several cancers," McKenna states.
Presently, the team are testing how saccharin and saccharin-based compounds affect breast and liver cancer cells. If these preliminary tests prove to be successful, the team could look to commence animal studies.
Previously at the 249th National Meeting & Exposition of the ACS, research was presented suggesting that vitamin D supplements could be used to slow or reverse the progression of low-grade prostate tumors.