Artificial sweetener may be key to treating cancer

A study presented at the 249th National Meeting & Exposition of the American Chemical Society shows that the artificial sweetener saccharin could potentially lead to the development of drugs capable of combating aggressive, difficult-to-treat cancers with fewer side effects.


The new work examines how saccharin binds to and deactivates carbonic anhydrase IX, a protein found in some very aggressive cancers. It is one of many driving factors in the growth and spread of such cancers in the breast, lung, liver, kidney, pancreas, and brain.

Carbonic anhydrase IX helps regulate pH in and around cancer cells, allowing tumors to thrive and potentially metastasize 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, making it a prime target for anti-cancer drugs that would cause little or no side effects to healthy tissue surrounding the tumor. However, carbonic anhydrase IX is similar to other carbonic anhydrase proteins that our bodies need to work properly.

In earlier work, Italian scientists 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, an Australian research team created a compound in which a molecule of glucose was chemically linked to saccharin. This 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.

Now, researchers at the University of Florida are using X-ray crystallography to determine 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. The researchers are currently testing the effects of saccharin and saccharin-based compounds on breast and liver cancer cells. If successful, these experiments could lead to animal studies.


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