Artificial Sweeteners May Lend New Cancer Treatments

Artificial sweeteners, and in reality, sweeteners in general, have received a lot of attention for their pros and cons: great for diabetics, great for weight management/loss, terrible for weight loss and food cravings, aggravating to metabolic disorders, cancer-causing, etc. The list goes on and on. But new findings presented on Tuesday, March 24, 2015, at the 249th National Meeting & Exposition of the American Chemical Society (ACS), found saccharin—the artificial sweetener that is the main ingredient in Sweet 'N Low®, Sweet Twin® and Necta®—could potentially lead to the development of drugs capable of combating aggressive, difficult-to-treat 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," said Robert McKenna, Ph.D., 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."

The new work examines how saccharin binds to and deactivates carbonic anhydrase IX, a protein found in some very aggressive cancers, according to a press release from ACS. It is one of many driving factors in the growth and spread of breast, lung, liver, kidney, pancreas and brain cancers. 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. 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 tumor. Unfortunately, there's a catch. 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—ironically, once considered a possible carcinogen—comes in.

In earlier work, scientists from a group led by Claudiu T. Supuran, Ph.D., University of Florence, Italy, discovered 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, Ph.D., at Griffith University, Australia, created a compound in which a molecule of glucose was chemically linked to saccharin. This small change had big effects. Not only did it reduce the amount of saccharin needed to inhibit carbonic anhydrase IX, 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. If successful, these experiments could lead to animal studies.

Although developing an anti-cancer drug from saccharin may not directly impact the food and beverage industries, it is good new for artificial sweeteners, the medical community and cancer patients. The state of sweeteners will continue to evolve as the science community explores their many benefits and uses.