Saccharin, an artificial sweetener once considered a possible carcinogen, could lead to the development of drugs that battle aggressive difficult-to-treat cancers, a new study has found.
"It never ceases to amaze me how a simple molecule, such as saccharin - something many people put in their coffee everyday - may have untapped uses, including as a possible lead compound to target aggressive cancers," said Robert McKenna at the University of Florida.
"This result opens up the potential to develop a novel anti-cancer drug that is derived from a common condiment that could have a lasting impact on treating several cancers," McKenna said.
The new work examines how saccharin binds to and deactivates carbonic anhydrase IX, a protein found in some very aggressive cancers.
Carbonic anhydrase IX helps regulate pH in and around cancer cells, allowing tumours to thrive and potentially metastasise to other parts of the body.
Because of this finding, the researchers wanted to develop saccharin-based drug candidates that could slow the growth of these cancers and potentially make them less resistant to chemo or radiation therapies.
Except for in the gastrointestinal tract, carbonic anhydrase IX is normally not found in healthy human cells.
According to McKenna, this makes it a prime target for anti-cancer drugs that would cause little or no side effects to healthy tissue surrounding the tumour.
Carbonic anhydrase IX is similar to other carbonic anhydrase proteins that our bodies need to work properly.
So far, finding a substance that blocks carbonic anhydrase IX without affecting the other ones has been elusive. And that's where saccharin comes in.
In earlier work, scientists at the University of Florence, Italy, discovered that saccharin inhibits the actions of carbonic anhydrase IX, but not the 14 other carbonic anhydrase proteins that are vital to our survival.
Building on this finding, a team led by Sally-Ann Poulsen at Griffith University, Australia, created a compound in which a molecule of glucose was chemically linked to saccharin.
This small change reduced the amount of saccharin needed to inhibit carbonic anhydrase IX and the compound was 1,000 times more likely to bind to the enzyme than saccharin.
Using X-ray crystallography, McKenna and his students Jenna Driscoll and Brian Mahon have taken this work a step further by determining how saccharin binds to carbonic anhydrase IX, and how it or other saccharin-based compounds might be tweaked to enhance this binding and boost its anti-cancer treatment potential.
McKenna's team is currently testing the effects of saccharin and saccharin-based compounds on breast and liver cancer cells.
The research was presented at the 249th National Meeting & Exposition of the American Chemical Society (ACS) in Denver.
